Numerous variants of squamous cell carcinoma (SCC) have been described. We recently encountered four examples of SCC composed primarily of single, atypical cells that were cytokeratin (CK) MNF116-positive and p63-positive. One case was particularly difficult to diagnose as the single cells were obscured by a dense inflammatory infiltrate. We have also noted similar single cell infiltration toward the periphery of four additional cases of more typical SCC. These foci resemble the single tumor cells that may infiltrate at the borders of spindle cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of these neoplasms. This single – cell pattern of SCC can easily be misdiagnosed, and CK MNF116 and/or p63 are diagnostically helpful in recognizing it.