Endometrial carcinoma (EC) and colorectal cancer (CRC) are closely linked in a well-documented, predominantly inherited cancer syndrome known as hereditary non-polyposis colorectal cancer (HNPCC). Epidemiological studies report that women with EC have a 1.5- to 3-fold increased risk of developing CRC. However, this elevated risk could be the consequence of genetic confounding. In order to plan a proper CRC prevention program, we sought to verify and quantify this risk, first estimating it in 697 women with EC who received treatment and follow-up in one health care district between 1986 and 2000. The standardised incidence ratio (SIR), which compares observed with expected cases of CRC in the general population, was calculated. Multiple logistic regression analysis was used to estimate the odds ratio and 95% confidence interval of a dependent variable, second primary CRC, as a function of clinical and pathological features. Multiple primary tumours were observed in 6.7% of the patients, with CRC being the second most frequently occurring type of cancer. The estimated overall risk for CRC was slightly higher than that observed in the general population, but was nonetheless not statistically significant. Multivariate analysis revealed a family history of CRC to be a risk factor for developing the disease as a second primary cancer. A BMI ≤25 and the pathological spectrum of EC were clinical and pathological features associated with CRC development, but were without statistical significance. MSH2 and MLH1 mutational screening confirmed genetic involvement in most of the CRCs observed in the cohort. Overall, the data show that women with EC have a CRC risk similar to that of the general population, and should therefore be screened on the basis of risk factors for CRC.