Despite the modest improvements in patient survival from colorectal cancer in the last few decades, the overall five-year survival rate remains at 40 to 45 percent. Surgical resection is the mainstay of treatment for colorectal cancer; however, nearly one-half of all patients who undergo a potentially curative resection will relapse because of undetected micrometastasis. The fact that the overall survival rate remains poor strongly suggests that the dissemination of these cells occurs early in the disease process and emphasizes the need for finding feasible diagnostic methods with sufficient sensitivity and specificity. The most commonly used technique for the detection of nucleic acid material of disseminated tumor cells is the polymerase chain reaction. We critically review the literature on DNA and messenger ribonucleic acid molecular markers that have been used for the detection of circulating tumor cells in the peripheral blood of patients with colorectal cancer and other solid tumors as appropriate for comparison. The cytokeratins, particularly cytokeratin 19 and cytokeratin 20, are the most investigated prognostic markers, but even for these questions remain about their clinical value, and hence most recent studies are utilizing a combination of factors. There is an urgent need for standardized isolation and analysis techniques to be adopted thus allowing large-scale, appropriately controlled, multicenter trials to be undertaken on the most promising candidate markers.