Conventional serum tumor markers (CSTM) are widely used for monitoring patients with cancer. However, their usefulness as a diagnostic tool is controversial in primary or metastatic liver cancer (PMLC).To evaluate the diagnostic performance of the most commonly requested CSTM in the diagnostic approach of PMLC.Review of medical records of patients aged over 18 years with a liver biopsy, attended from 2005 to 2017 in a tertiary hospital and a regional cancer center in Colombia. The results of liver biopsies were compared with tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 125 and prostate specific antigen (PSA) using a receiver operating characteristic (ROC) curve analysis.We reviewed 2063 medical records and retrieved 118 eligible patients (59 cases and 59 controls, 70% males). Thirty percent had obstructive jaundice. There was heterogeneity in the amount of tumor markers requested according to medical criteria. Only CA 19-9 showed discriminative capacity (> 17.6 U/m), with a cut-off point lower than that reported in the literature and a sensitivity of 69.5%, specificity of 91.6%, a positive likelihood ratio (LR) of 8.32, and a negative LR of 0.33.Except for CA 19-9, tumor markers were not useful for the initial diagnostic approach in patients with suspected primary or metastatic malignant liver tumors.