Colorectal cancer is currently one of the most common malignancies in both men and women. Surgical resection remains the essential element in the local control of the disease but the development of novel diagnostic and therapeutic tools can enhance the results of radical surgery. The indication for adjuvant treatment majorly depends on a correct pathological assessment of the surgical specimen - a correct pTNM staging. For patients diagnosed with stage III disease (characterized by the presence of lymph node metastases), adjuvant chemotherapy increases the survival rate, while in stage II disease, in most cases, the chemotherapy is contraindicated, due to increase morbidity without real benefit. This is why an accurate pN stage becomes essential. It is proven that classic pathological exam sometimes fails to identify lymph node micrometastases or isolate tumor cells, which might explain local or distant relapses in stage II patients. In our study, we evaluated a total of 39 surgical specimens of cTNM stage II patients operated for colon or rectal cancer. In the attempt to enhance the accuracy of pTNM staging we used ex vivo lymph node mapping combined with sentinel node analysis on serial sections in both classical histological and immunohistochemical (IHC) staining. We have demonstrated that the IHC staining on sentinel lymph node can improve the accuracy of pTNM staging, when used as a complementary diagnostic test, by identifying micrometastases and isolated tumor cells.