In the present work we investigated the possible role of the native fluorescence of blood plasma in the management of colorectal cancer (CRC) and its feasibility as a new tumor marker. Sample of blood was collected from 248 asymptomatic blood donors and from 246 CRC patients. The native fluorescence of blood plasma was measured using a conventional spectrofluorimeter. The intensity of fluorescence of blood plasma at 623 nm (IF623), reasonably ascribed to endogenous porphyrins, was significantly higher in CRC patients than in healthy subjects. The diagnostic capability of IF623 in the discrimination between healthy subjects and CRC patients was tested by Receiving Operating Characteristic (ROC) curve analysis, which resulted in an Area Under the Curve (AUC) of 0.72+/-0.01. Fluorescence measurement of blood plasma might be considered diagnostically useful as a candidate for a new tumor marker for CRC management. The procedure is characterised by a great acceptability and by a very low cost, and might be used in a two-step screening wherein an IF623 positive result is followed by colonoscopy.