The aims of the present study were: (i) to describe the KRAS mutation spectrum in a consecutive series of CRC specimens (n = 314) referred to our laboratory for KRAS mutation analysis during the last two years; (ii) to evaluate the performance of Pyrosequencing compared to allele-specific PCR (DxS) on the samples (n = 56) that originated from tissues with a low tumor cell count; and (iii) to evaluate the new CE-IVD-marked versions of these techniques on a selected subset (n = 100) of the specimens. The gene discussed is KRAS; the disease is colorectal carcinoma.