There are very few studies about K-ras mutations in colorectal cancer (CRC) from developing countries such as Iran. It is therefore essential to conduct studies to learn about the molecular signature of such tumors, allowing the determination of an appropriate management plan. In the present study, we aimed to determine the frequency and types of K-ras mutations among patients with CRC in Iran.Formalin-fixed paraffin-embedded specimens of 100 cases of CRC were collected from hospitals affiliated with Shiraz University of Medical Sciences (June 2011 to June 2013). All of the H&E slides were examined and proper slide with a minimum of necrosis and maximum of well-preserved tumor cells (at least 70% tumor in each slide) were selected. Recurrent, metastatic, and post chemotherapy cases were excluded from the study. Mutation of codons 12 and 13 of K-ras gene by PCR was performed, followed by direct sequencing by Sanger method.From 100 eligible cases (55 male and 45 females with mean age of 59 years), 32% had mutant K-ras gene; the most common substitution was 12G>C followed by 12G>A and 13G>A, respectively.It is found that K-ras mutation rate, among the selected population of the southern province of Iran, was as high as 32% (codon 12: 71.8% and in codon 13: 25% and one in both codons: 3.1%).