TP53 and KRAS mutations are commonly found in colorectal tumors. The rates of mutation of these two genes in colorectal carcinoma were compared to better understand their contribution to the disease. Here, colorectal tissue samples were obtained from 49 patients with colorectal adenoma, 90 patients with single primary colorectal carcinoma, 32 patients with multiple primary colorectal carcinoma, and 50 healthy individuals. Real-time PCR was used to amplify exons 5-8 of TP53 and codons 12-13 (exon 1) of KRAS from each sample. Clinical and pathological features of tumor samples were recorded, and these features were compared against mutation status using multivariate logistic regression. The proportions of samples with mutations of KRAS and/or TP53 were significantly different between control individuals and those with colorectal lesions (P < 0.05). Indeed, more than 80% of carcinoma samples were positive for either a KRAS or TP53 mutation. Further, mutations in KRAS and/or TP53 were significantly more common among the two groups with confirmed carcinoma than in individuals with colorectal adenoma (P < 0.05). Interestingly, TP53 mutations were significantly more frequent than KRAS mutations in the colorectal adenoma group (P < 0.01). However, no associations were observed for the frequency of KRAS or TP53 mutations between well-differentiated and poorly-differentiated tumors, different tumor stages, or other clinical and pathological features like age, sex, family history, tumor location, and stage and grade of differentiation. In conclusion, KRAS and TP53 mutations are important contributors to colorectal cancer, and TP53 mutation appears to occur earlier than KRAS mutation.