The concept of clinicopathologic dissociation is a neglected one in medicine. It refers to the unexpected, complete absence of concordance between the clinical picture and the underlying histopathologic finding. The recognition of such a phenomenon generally implies radically different treatment and follow-up choices. A rare phenomenon, it can however be encountered, especially in the field of dermatoncology and dermatology at large. It should be kept separate from clinicopathologic discordance or discrepancy, the term used by surgical pathologists to indicate the lack of expected molecular markers or to the presence of unexpected ones in the face of a given morphological diagnosis, albeit overlaps occur. More generally, the concept of clinicopathologic dissociation can be applied when a given clinical manifestation appears completely unrelated to the underlying objectively tracked primary disease. Examples are provided, and educational, ethical and medicolegal implications are briefly discussed.