The SW480 and SW620 colon carcinoma cell lines derive from the primary tumour and a lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed the SW480 and SW620 cytoskeleton remodelling by measuring the cells mechanics and morphological properties using different microscopic techniques. We observed that the different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist to shear forces of the stream of cells derived from the lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with the stiffness and the adhesion between the AFM tip and cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by the colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.