Background/Objectives: Non-melanoma skin cancers (NMSC) are the most frequent cutaneous tumors globally. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most frequently encountered representatives of this group and may represent a diagnosis challenge in some circumstances of hard to differentiate tumors. The aim of this study was to determine the factors that influence the diagnosis of NMSC and their impact. Methods: A single center, descriptive, retrospective study was performed, with a total of 866 cases from 678 patients from 2016-2022. Cases were then analyzed based on their histological diagnosis and characteristics and the available clinical data. Results: From the 866 cases, 709 were histologically diagnosed as BCC and 157 as SCC. The clinical accuracy for BCCs was 95% whereas for SCCs was 62% with both having large variations among attending dermatologists. Clinical factors that were found to influence the diagnosis were: advanced age (p<0.001), a biopsy beforehand (p=0.009), and multiple diagnosis or uncertainty (p=0.005) were predictive for a final diagnosis of SCC. Factors predicting BCCs were: the presence of multiple lesions (p=0.032), presence of ulcerations (p<0.001), age under 50 (p=0.002). BCCs were more likely to be correctly diagnosed than SCC (p<0.001). Cases with multiple BCCs were thinner compared to single-lesion excisions (p<0.001). A tumor reduction was observed after the 2020 the SARS-CoV-2 (p=0.023). Conclusions: Differentiating NMSC can be challenging, but several trends have been observed which may aide in further improving the diagnosis rates especially for SCCs.