The rates of colorectal cancer (CRC) interval surveyed in screen-detected patients using a fecal immunochemical test (FIT) are not negligible. The aim of this study was to assess the effect of interval cancer on outcomes compared with a population with cancer diagnosed after a positive test result. All patients between 50 and 71 years of age, who were residents of the Mantua district, affected by CRC and operated on from 2005 to 2010 were reviewed. Other than patient-related, disease-related, and treatment-related factors and tumor location, this population was differentiated as either participating or not to screening and then into populations developing interval cancer after a negative FIT result. Mortality was investigated by univariate analysis and by overall survival rates. The mean age of the 975 patients enrolled was 62 years (61.7% males). Most patients (n=575, 59%) were not screen detected, and 400 (41%) were screen detected. Fifty-six (5.7%) patients in the latter group, representing 14% of the participants, developed interval cancer after a negative FIT result. Their cancer was mostly localized in the right colon (41.1%) instead of the left colon and rectum (P=0.02). They also showed higher stages (P=0.001), a moderate degree of differentiation (P=0.001), and overall higher mortality rates than patients with cancer diagnosed after a positive test result (P=0.001). The effect of interval CRC after screening with FIT resulted in worse outcomes compared with the FIT-positive group. With such findings, patients who had negative results for FIT should be informed of the risk of developing cancer within the rounds of screening to independently gain educational skills in the area of health prevention.