The human lectin galectin-7 (Gal-7; p53-induced gene-1) has anti- and pro-malignant features in different in vitro models. We tried to clarify relation of its expression to cellular and clinical parameters in head and neck squamous and basal cell carcinomas. Using a non-cross-reactive antibody, immunohistochemical staining in squamous cell epithelia (epidermis, epithelium of oropharynx and larynx) (n = 57), squamous cell carcinomas (n = 47) and lymph node metastases (n = 25), as well as basal cell carcinomas (n = 10) were studied. This monitoring was flanked by processing to assess the level of differentiation (cytokeratins 10 and 14), proliferation (Ki67) and basal lamina formation (collagen IV). The results were correlated with clinical and pathological findings (grading, TNM-staging, extracapsular spread, angio- and lymphangioinvasion, perineural invasion, recurrence and survival). Gal-7 resides in all layers of epithelia with cytoplasmic and nuclear localization in normal specimens. Basal cell carcinomas were devoid of the Gal-7 respective signal. Squamous cell carcinomas were positive, presenting different staining profiles. Intense staining was predominantly found in squamous cell cancers with high degrees of differentiation and keratinization. Fittingly, poor level of differentiation (P = 0.0009), absence of keratinization (P = 0.0105) and significant discontinuity or absence of collagen IV expression in the peritumoral basal lamina (P = 0.0024) was found in Gal-7-negative tumors. Gal-7 presence was not related to gender, primary tumor site, T-stage, N-stage, clinical stage, extracapsular spread, angio- and lymphangioinvasion, perineural spread or treatment outcome at a statistically significant level. Immunohistochemical analysis revealed a positive correlation for differentiation and keratinization to Gal-7 presence in squamous cell carcinomas. Absence of Gal-7 expression was detected in basal cell carcinomas. These clinical data delineate Gal-7 influence on differentiation in vivo, without evidence for a role in dissemination reported for lymphoma.