CSMD1 is a candidate tumor suppressor gene that maps to chromosome 8p23 that codes for a novel multiple domain complement regulatory and adhesion protein. To determine whether mutations in CSMD1 affected tumor development or patient outcome, we used nucleotide sequencing to identify single nucleotide polymorphisms in the CSMD1 gene of either tumor or matched normal tissues of 80 unrelated patients (30 colon cancer, 50 breast cancers). More than 92% of the 165 SNPs detected were present in the normal tissues. One non synonymous SNP found at an amino acid position 2772 in exon 55 of CSMD1 gene of a stage III, node positive colon cancer patient was of particular interest since it would result in a glycine to serine amino acid change at this position in the CSMD1 protein. This amino acid change was predicted to affect protein function by the SIFT (Sorting Intolerant from Tolerant) program. This SNP was found in the 19th Sushi domain of the CSMD1 gene and would be present in all three major isoforms of the CMSD1 protein. We predict that this particular polymorphism could affect tumor development and progression of cancer. It is a rare polymorphism found in <1% of the alleles studied. We have also found 40 synonymous and another 26 non synonymous SNPs which may impact the patient’s outcome for cancer.