SummaryBackground: Colorectal cancer (CRC) is an important oncological and public health problem worldwide, including Serbia. Unfortunately, half of the patients are recognized in an advanced stage of the disease, therefore, early detection through specific tumor biomarkers, such as carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA 19-9), is the only way to cope with CRC expansion.Methods: Our cross-sectional study evaluated the influence of some clinical, endoscopic and histological characteristics of CRC on CEA and CA 19-9 serum levels, to determine whether these biomarkers could be related to CRC detection. The study included 372 participants: 181 suffered from CRC and 191 participants were controls. Endoscopic and histological examinations were used for CRC diagnosis, while additional ultrasound and abdominal computerised tomography imaging were used for staging the disease. Measurement of CEA and CA 19-9 was performed after CRC confirmation.Results: Age, gender, tumor localization, macro-morphological and histological characteristics did not influence biomarkers serum levels. Both were significantly higher (p<0.01) in patients with Dukes D stage of CRC compared with controls. Sensitivity (76.8%) and specificity (76.6%) of CEA alone were higher than for CA 19-9, but with no statistical significance. Furthermore, sensitivity of CEA alone in the Dukes A/B group was similar to the entire CRC patient group.Conclusions: Although not recommended as a screening method for the general population, elevated values of each biomarker indicate further diagnostic procedures and their simultaneous testing can improve the diagnostic sensitivity in early detection of CRC, as shown by the united analysis (AUC 0.842).