Recent studies from mouse mapping studies for cancer susceptibility have successfully led to the identification of a handful of susceptibility genes. Ptprj was identified as a strong candidate gene for mouse locus susceptibility to colorectal cancer 1, and one variant, rs1566734, showed evidence of preferential allelic imbalance in human colorectal tumors. Haplotypes in human PTPRJ have also been associated with protective effects for breast cancer risk. To determine if variants or haplotype in PTPRJ confer protective or risk effects for colorectal cancer (CRC), we genotyped rs1566734 and six additional PTPRJ haplotype tagging single nucleotide polymorphisms (SNP) in CRC cases and controls from the Molecular Epidemiology of Colorectal Cancer study. There was no evidence for cancer risk with rs1566734 in 1,897 cases and 1,954 controls with a homozygote odds ratio of 1.09 and 95% confidence interval of 0.85 to 1.39. The 6 tagging SNPs resulted in 6 main haplotypes (frequencies, >1%). None of the six tagSNPs individually showed significant evidence for risk; however, rs1503185 showed a nonsignificant protective effect. One haplotype was overrepresented in cases compared with controls, corresponding to a 34% increase in risk CRC, but there was no significant difference overall in haplotype frequencies between cases and controls (global test P statistic=0.19). From this study, we observe no significant increase in risk for human CRC with variants or haplotypes in PTPRJ. Additional studies are warranted to study possible PTPRJ-interacting loci, which are observed with Scc1 in the mouse models for CRC susceptibility.