Objective: To evaluate head and neck squamous cell carcinomas (SCCAs) for the expression of nerve cell adhesion molecule (N‐CAM). We propose that expression of N‐CAM by tumor cells may be associated with perineural invasion in SCCA of the head and neck. Methods: Seventy‐six archived specimens of histologically proven SCCA were analyzed by immuno‐histochemistry for the expression of N‐CAM. Positive and negative controls were used to assess staining. Two sections of each specimen were reviewed for the presence of perineural invasion. A retrospective chart review was performed for each patient that corresponded to the above specimens. Results: Perineural invasion was present in 28 (37%) of the 76 patients evaluated for the expression of N‐CAM. N‐CAM expression was demonstrated in 38 (50%) of the 76 specimens. The incidence of N‐CAM expression was significantly associated with perineural invasion (P = .002). There was no significant association between the presence of staining or the presence of perineural invasion and the incidence of locoregional recurrence, distant metastasis, or survival status; however, the mean follow‐up was only 13.6 months (range, 1–49 mo). Conclusion: There is a positive correlation between the presence of N‐CAM expression and perineural invasion in SCCA of the head and neck. The expression of this adhesion molecule by tumor cells may facilitate both homophilic cell‐to‐cell and heterophilic cell‐to‐substrate adhesion, thereby enabling the tumor cells to use the perineural tissues or neural cells, or both as a conduit for perineural spread.