Background: Non-melanoma skin cancer (NMSC) is the most common malignancy in Caucasians. It mainly includes two major keratinocyte tumors – basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The objective of the study was to analyze and compare the clinicopathological differences between patients with BCC and SCC of the skin. Material and Methods: A cohort of 541 patients with a total of 719 BCCs, and 126 patients with a total of 162 SCCs were retrospectively analyzed. Results: While there was virtually the same proportion of men (49.91%) and women (50.09%) in BCC patients, SCCs occurred more frequently in men (68.2%) than in women (31.8%). The mean age of the individuals with BCC and SCC was 70.8 and 78.2 years, resp. The number of BCCs rises from 50 years of age and this increase showed a linear trend up to 80 years, subsequently followed by decline. SCC lesions occur more rapidly from 70 years of age followed by a sharp increase that exhibited an exponential relationship. BCCs and SCCs occurred predominantly on the head and neck region, comprising a total of 69.8% and 81.4% of the cases, resp. However, BCC lesions were seen more often on the face and SCC lesions were diagnosed more frequently on the extra-facial parts of the head. Further, BCCs occurred more frequently on the trunk, and particularly on the back, compared to SCCs. Conclusion: Although BCC and SCC are covered under common term NMSC, they manifest several clinicopathological differences. Despite sharing common etiologic determinants, at least from the onco-epidemiologic perspective, they should be considered separately.