The aim of this paper was to examine the distribution of fecal hemoglobin (f-Hb) concentration in a Spanish colorectal cancer screening population according to sociodemographic characteristics and analyze whether f-Hb was associated with clinical outcomes (type of lesion and its location). From September 2009 to November 2012, we sent 77,744 invitations to individuals aged 50-69 years to provide one sample of feces. f-Hb was measured on samples from 27,606 screenees (35.5%). Colonoscopy findings and pathology data were collected on the 1406 screenees with f-Hb greater than 100 ng Hb/ml (20 mg Hb/g feces). The Mann-Whitney U-test and the Kruskal-Wallis test were used to compare f-Hb (median) according to sociodemographic variables, clinical outcomes, and histological features of adenomas. f-Hb from greater than 100 ng Hb/ml was categorized into quartiles. Regression models were used to determine whether f-Hb was a risk predictor of colorectal lesions. f-Hb was associated directly with the severity of the colorectal lesions. An overlap between individuals with a negative colonoscopy and those with a low-risk adenoma was observed. High-grade dysplasia, villous histology, distal location, and increasing size were all features associated with an increased f-Hb level. f-Hb could be used in individual risk assessment to determine surveillance strategies for colorectal cancer screening.