 Since there was little understanding about what stains bound to, skeptics often raised doubts that they were revealing actual structures in cells. Bechtel (2000, 2006) highlights three considerations that often figured in scientists’ evaluation of whether micrographs were informative about cells or only artifacts of the methods of preparation: (1) the quality of the micrographs themselves—do they exhibit distinct patterns? (2) the robustness of the results—can comparable results be generated with different techniques (e.g., with light and electron microscopy or with multiple stains)? and (3) the theoretical plausibility of the results—do they fit into a coherent theoretical account? While the first is seldom commented on in philosophical accounts, it is notable that scientists are inclined to assume that if an image reveals a distinct, replicable pattern, it reflects something in the source (although this assessment may be retracted if, for example, a researcher shows how the pattern could be generated by other means). There has been extensive philosophical discussion of the second—the inference that when the same result is generated by independent means, it reflects a preexisting entity in the world (Hacking 1983; Culp 1995; Stegenga &amp; Menon 2017). However, this criterion proves insufficient at just the point at which results with new techniques, such as the electron microscope, are most controversial—when the images contain structures beyond those that can be detected with other existing techniques. In these cases, the distinctness of the patterns together with considerations as to the theoretical plausibility of the findings are the criteria researchers can use. Appeal to theoretical plausibility, however, would seem to be circular since in traditional philosophical accounts, theories are tested by the evidence generated by the technique. But developing a plausible theory that fits with an experimental finding and other evidence is not easy and when they are able to do so, scientists view it as buttressing their judgments that the images reflect real structures. To illustrate how these considerations have been invoked in in cell biology, we present two examples philosophers have examined of conflicts over whether the structure shown in microscopic images was real or an artifact. The cases ended differently, one with the acceptance of the structure, one with its rejection.