Introduction: The proto-oncogene c-Kit encodes a tyrosine kinase receptor which is essential during embryonic and postnatal life but its expression in precancerous lesions has not been studied. Musashi-1 was initially identified as a neuronal stem cell marker and recently as an intestinal stem cell marker and is aberrantly expressed in several cancers including colorectal cancer, but its role in neoplastic tissues has not been elucidated. The present study aims to study the expression of c-Kit and Musashi-1 in precancerous lesions and colorectal carcinoma in correlation with etiological factors. Methods: Immunohistochemical analysis, western blot and RT-PCR were done to observe the expression of c-Kit and Musashi-1 in normal, ulcerative colitis, adenoma and adenocarcinoma of colorectal tissues. Results: c-Kit expression was observed to decrease from normal to adenocarcinoma. In contrast, Musashi-1 showed increased expression from adenoma to carcinoma stages. Furthermore, c-Kit showed statistically significant association with alcoholic and non-alcoholic patients (p < 0.03*) and Musashi-1 had statistically significant association with age (≥ 60 and < 60) (p < 0.005*), gender (p < 0.02*) and alcoholics (p < 0.001**). However, statistically significant negative correlation was found between the expression of c-Kit and Musashi-1 in colorectal carcinoma. Conclusions: Overall, these studies indicate that the decreased or loss of c-Kit and increase in the Musashi-1 expression in carcinoma can be attributed to the disease progression and malignant transformation of colorectal epithelium. A statistically significant negative correlation was found between c-Kit and Musashi-1 in colorectal carcinoma.