The expression of neural cell adhesion molecule (NCAM) was analyzed in immunohistochemical preparations from adenoid cystic carcinoma. The goal was to evaluate whether NCAM expression could be used as a biological marker for the perineural invasion of adenoid cystic carcinoma in the head and neck. The presence of perineural invasion and NCAM expression was evaluated in samples from 49 patients. Perineural invasion was identified in 33 of them (67%). A high incidence of perineural invasion was found in adenoid cystic carcinoma in the parotid, hard palate, maxillary sinus and oral cavity. Positive NCAM staining was observed in 28 of 49 patients (57%). Of the 28 patients with NCAM staining, perineural invasion was identified in 24 (86%). In contrast, only 9 (43%) of the 21 tumors without NCAM staining had perineural invasion. The difference in NCAM expression between cases with and without perineural invasion was statistically significant (p< 0.01). When positive NCAM staining was used to estimate the presence of perineural invasion, the sensitivity was 73 and the specificity 75%. Histopathologic nodal involvement was found in 6 of 18 cases in which neck dissection had been performed. All 6 cases displayed positive NCAM staining, and 5 displayed perineural invasion in the primary adenoid cystic carcinoma. In conclusion, NCAM expression can, to a certain extent, be used as a predictor of perineural invasion in adenoid cystic carcinoma. Moreover, lymph node metastases could serve as a clinical indicator for perineural invasion and for NCAM expression.