Despite thousands of studies about colorectal cancer (CRC) as much as extensively usage of prognostic antibodies÷genes and clinical trials that include the newest targeted drugs, this tumor still remains in the top of both incidence and cancer-related mortality. In this review, we intended to correlate our experience in field of colorectal cancer with the literature data and to present our vision about the prognostic and predictive role of some of the most used molecular and immunohistochemical examinations in the field. The prognostic and predictive values of parameters such as microsatellite instability, angiogenesis, Maspin gene/protein, K-ras and BRAF mutations are discussed in relationship to the classical antibodies such as Keratin 7/20, p53 or HER2. At the end, we correlated these informations and tried to realize a molecular classification of colorectal cancer, similar to breast carcinomas, in order to establish targeted groups of patients for targeted therapy.