Objective: To investigate the prognostic value for loss of heterozygosity (LOH) of chromosomes 4 and 14q in early-stage colorectal cancer (CRC). Methods: A total of 70, largely microsatellite stable, tumours and their corresponding normal mucosa were subjected to microdissection and analysed for LOH at chromosomes 4 and 14q by using 13 highly polymorphic microsatellite markers. LOH was correlated with the survival of the patients, using univariate, multivariate and Kaplan-Meier's survival curves. Result: LOH at D4S2935, D4S1579 and D4S1595 on chromosome 4 was significantly associated with metastatic recurrence of early-stage CRC. For chromosome arm 14q, two minimal regions of deletion were associated with metastatic recurrence and mapped to neighbouring markers D14S275/D14S49 at 14q12-13 and D14S65/D14S250 at 14q32. High-level loss (loss of five to eight of the informative microsatellite markers) on both chromosomes 4 and 14q, to be an independent prognostic indicator in early-stage CRC was shown by multivariate analysis. Conclusion: Determining the LOH of chromosomes 4 and 14q and their extent in primary tumours of patients with early-stage CRC may constitute a molecular signature of metastatic recurrence. This may be achieved if new finding sheds light on the treatment of this subgroup of patients that have been largely ignored.