Non-melanoma skin cancer is the most common cancer in the world. Somatic mutations in the TP53 gene are associated with the development of this cancer. To describe mutations in exons 5-8 of the TP53 gene in a sample of Colombian patients with non-melanoma skin cancer.One hundred and fifteen patients with non-melanoma skin cancer were included. Exons 5-8 were amplified and analyzed by PCR-High Resolution Melting and Sanger sequencing.Fifty-seven patients with basal cell carcinomas and 58 with squamous cell carcinomas were studied. 16% of patients with basal cell carcinoma and 26% of patients with squamous cell carcinoma had mutations in the TP53 gene. The most frequent mutations were substitutions, while three patients had deletions. The most frequent mutation was p.R158G.The analysis showed that Colombian individuals with non-melanoma skin cancer have genetic TP53 variants different from those reported as recurrent for this disease.