After i) identification of MLH1-SPTAN1 protein-protein interaction [12], ii) knowledge of MLH1 capacity to stabilize its partner proteins [26,27] and iii) indications that MLH1 deficient tumors are less aggressive and distant metastasis are less common than in MMR proficient forms [28,29], we propose a MLH1 dependent role of SPTAN1 for cellular motility, metastasis and aggressiveness of CRC. The gene discussed is MRC1; the disease is colorectal carcinoma.