Both too cautious AND not cautious enough: "I'm skeptical that those are aliens, so I'm going to try pulling off their masks."
This comic depicts a table of possible responses to new information on the possibility of alien life. It is presented in table form, with the columns representing three levels of caution in reaction to new evidence, and the rows representing the strength of new evidence, increasing down the table. Each intersection then shows a small scenario of what the response would be. The left-hand scenarios are extreme in their enthusiasm for alien life, but not out of the possibility space of reactions (at least for sensationalist headlines). The right-hand column scenarios are hyperbolic. The center column represents a reasonable course of action.[citation needed] When read from left to right, top to bottom, the bottom right panel is the punchline. The joke comes from the ambiguity of the term "caution" in the column headers: when presented with definitive evidence of alien life in the form of a first contact situation, caution no longer refers to confidence in your results, but rather to the level of precautions taken against potential physical harm... unless you're the pair of people in the bottom right corner, who are so cautious in their assessment of alien life that they fail to take necessary caution for their own safety.
This comic was a reaction to the discovery of phosphine gas on Venus, which is where Ponytail's "V" figure in the second row comes from (a representation of the phosphine absorption feature). Phosphine is a molecule whose presence in the Venusian atmosphere came as a surprise. Light breaks phosphine down, meaning something must be producing it. However, there is no known abiotic mechanism on Venus that would produce the gas in the quantities observed. The phosphine could therefore be a sign of life on Venus, but more evidence is needed. Venus was also an unexpected place to find a possible sign of life — although it was a common pulp fiction setting in the early 20th-century, the arrival of the space probe era dashed hopes that the hidden surface might be, say, an exotic jungle (one of the more common pulp-fiction concepts). More recent efforts at finding life in the Solar System have mostly focused on Mars and various ice moons with suspected subsurface oceans, but life more-or-less as we know it could exist within the upper atmosphere of Venus, which has more Earth-like conditions than the surface.
Description of responses
In the first row, an asteroid looks like an "alien probe". This is based on a real observation and the responses to it: in 2017, 'Oumuamua passed through the solar system, with a hyperbolic trajectory that indicated interstellar origin. 'Oumuamua had an elongated shape and a slight acceleration not caused by gravity, which caused wild speculation as to the nature of our interstellar visitor. The "least cautious" response (which was seen many times, but not from serious astronomers) immediately jumps to the conclusion that the asteroid is an alien probe similar to the one presented in the science fiction classic Rendezvous with Rama. "Appropriate caution" causes the second observer to seek to discover more pertinent information about the asteroid. Some humor is derived from the "appropriately cautious" response including a firm and unambiguous "it's not aliens". The "too cautious" response simply ignores the asteroid's interesting properties and instead diverts either into a Socratic assertion or some other less relevant form of philosophical doubt. The image of an astronomer looking through a telescope and being alarmed by seeing "something huge" which is actually very small and very close is an old comic gag and is given very similar to the wording of a memorable scene from a comedy show, but not something that should happen in real life thanks to parallax.
The second row refers to the discovery of phosphine gas on Venus, with the "least cautious" response to simply conclude that there is life on Venus. The "appropriately cautious" response considers several possibilities, and calls for more research. The "too cautious" response adds nothing at all to our understanding of Venus, comically understating the significance of the find beyond any point of usefulness (all atmospheres contain molecules; it's what makes an atmosphere an atmosphere and not a vacuum).
In the final row, aliens have arrived on Earth. There is no longer reason to question the evidence of them. The insufficiently cautious approach is to immediately hug them. Most humans would not take kindly to being hugged without warning or consent by a stranger, and an alien's reaction is impossible to predict. If the aliens are peaceful, Cueball could easily be causing a diplomatic crisis or exposing himself to unintentional danger. If the aliens are here to hunt or otherwise make war, he has likely just gotten himself killed. The more responsible approach is to consider ways to communicate at a distance. By doing so, the humans in this panel are attempting to maximize the benefits of first contact while minimizing the hazards. In the punchline panel, the United Nations building is being vaporized by flying saucers with energy beams; the aliens are proving to be dangerous and warlike. But rather than focus on that, "overly cautious" Megan and Cueball are still focused on whether or not they can say with confidence that the aliens exist. Though in one sense it could be reasonable to not embrace the 'aliens' explanation immediately (the UFOs could be of human origin), their phrasing makes it clear that this is not their reasoning. By referring to the energy beams as "possible biosignatures" they make it clear they do not believe the beams are of terrestrial origin. The fact that they are even discussing this when they should be running for their lives is excessively pedantic to an absurd degree.
The destruction of human governmental buildings is a common trope in science fiction, both as a way for the aliens to show their military supremacy, and as a way to interfere with the ability of humanity to co-ordinate a response to an attack. The United Nations building is allegedly the co-ordination centre for a worldwide response to an extraterrestrial incursion, so it makes sense for the aliens to attack it. They also might be launching simultaneous attacks on all major governmental centers in the world.
Title text
The title text refers to an action which is simultaneously too cautious and not cautious enough: the speaker is skeptical that aliens exist, which is usually an appropriate belief, except that Megan and Cueball are in the situation presented in the bottom row, where aliens have landed right in front of them. Rather than modifying his belief (presumably it's Cueball, who was the one to approach the aliens in the other panels), he expresses an intention to approach the alleged aliens and attempt to remove their masks. He believes that he will expose a human wearing a costume, perpetrating a "Scooby-Doo"-style hoax, but no matter what the outcome is, he's acting rashly. If the beings before him are aliens, he will be initiating a very aggressive first contact and will likely receive a violent response, and even if the alien is not violent, Cueball might end up removing an environmental apparatus that is protecting it from Earth's environment (or vice versa). On the other hand, if the "aliens" really are fakes, Cueball might end up injuring someone who is just playing a harmless joke (and who'd want to keep some kind of mask on to reduce the spread of COVID-19), or he might end up getting injured by a violent response.