Studies on melanoma cell lines indicate the expression of actin-binding protein (ABP), a peripheral cytoplasmic protein that crosslinks actin, is important for melanoma cell motility. We used an ABP-specific monoclonal antibody to characterize ABP expression in 18 benign nevi and 28 primary and metastatic malignant melanomas. Heterogeneous expression of ABP staining was observed in metastatic melanoma. No clear differences in ABP staining were identified among compound nevi, dysplastic nevi, and superficial spreading melanoma; however, the lentiginous intraepidermal component of the benign and malignant lesions and the pagetoid cells of superficial spreading malignant melanoma were negative for ABP. In contrast, the nested intraepidermal and dermal components of both benign nevi and primary malignant melanoma were positive. The differential expression of ABP of the lentiginous component as opposed to the intraepidermal nests and pagetoid cells of benign nevi or melanoma may represent a capacity of the nested melanocytes to migrate from the epidermis to the dermis during maturation or invasion. Taken together, the findings support that ABP may be important for cell-cell adhesion during tumorigenesis and may play a role in tumor cell ameboid motility during tissue invasion.