The prognosis of patients with rectal cancer can be assessed mainly on the basis of clinical and pathological factors among which the pTNM stage is the most valuable indicator. Recently, different combinations of molecular markers, which have prognostic significance, have been identified in an attempt to establish a "molecular staging" that would permit - along with the histopathological staging - taking optimum therapeutic decisions in colorectal cancer. An example in this respect is the attempt to classify patients with rectal cancer stage II (N-) with a view to administering adjuvant treatment to the risk subgroup. The prognostic role of various factors (biological, genetic, molecular, etc.) was classified into four categories according to their predictive value. This paper reviews the most recent research, especially regarding the factors in the third category in order to assess their impact upon prognosis and to identify the most valuable factors that could change the therapeutic algorithm of rectal cancers in the future. However, more statistical studies are necessary before these factors can become the basis of new therapeutic strategies or prognostic evaluations in rectal cancer.