Keratoacanthoma is a unique clinicopathological entity, despite a recent trend to regard it as a variant of squamous cell carcinoma. The occurrence of perineural invasion is an uncommon phenomenon in keratoacanthomas, with a predilection for lesions on the face. We studied a series of 40 cases of keratoacanthoma in which perineural invasion occurred. Of the 40 cases, 27 were from the head or neck region. We found no metastasis or direct death attributable to the presence of perineural invasion in the 35 cases in our series for whom follow-up data were available. In only one case did local recurrence occur and this was not considered by the authors to be directly attributable to the presence of perineural invasion. These findings add further support to the notion that keratoacanthoma is biologically different from squamous cell carcinoma.