Background: Despite several studies have evaluated the role of prognostic factors (PF) in metastatic colorectal cancer, results are controversial. The aim of the present study was to assess PF in a homogeneous population with MCCID treated with biochemical modulation of 5- Fluorouracil-based regimens. Methods: Analyses were based on individual data of 318 patients (P) with MCCID treated in different prospective trials at GOCS Institutions since May 1984 to Jun 2001. The following variables (V) were considered: a) Clinical variables (CV): age, sex, family history of CC, hypertension, diabetes, tabaquism, weight loss, and performance status (PS), b) Tumor variables (TV): histologic grade, size and location of primary tumor; number of metastatic sites, number and size of liver metastases, uni- bilateral liver involvement; and c) Laboratory variables (LV): CEA, lactate dehydrogenase (LDH), alkaline phosphatase, ALT, AST, and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. A Cox’s proportional hazard modeling was used for multivariate analyses. Results: The OS for the entire group was 18.1 months (IC95, 15.0–22.7). Univariate analysis showed statistical significance in the following; a) CV: family history CC (p=0.001), PS (p=0.04), diabetes (P=0.003); b) TV: histologic grade (p=0.01), uni-bilateral liver involvement (p<0.0001), number of liver metastases (p<0.0001) and size of liver metastases (p<0.0001); and c) LV: hemoglobin (p=0.05), ALT (P=0.0006), AST (p<0.0001), alkaline phosphatase (p<0.0001), LDH (p=0.0004); Cox’s analyses showed statistical significance only for PS and alkaline phosphatase (p= 0.01 and p=0.0001, respectively). Conclusions: In this setting of P with MCCID the PS remains the most important PF for OS. High value of alkaline phosphatase may reflect liver involvement. No others PF considered in the analyses had prognostic influence.