However, this conclusion is limited by the low number of samples employed that will be increased in the next external quality assessment, which will also include samples with low percentage of tumor cells. biological material for molecular analysis, the extraction of DNA, and the methods for the mutational analysis that are summarized in this paper. Following the publication of the guidelines, the scientific societies started an external quality assessment scheme for KRAS testing. Five CRC specimens with known KRAS mutation status were sent to the 59 centers that participated to the program. The samples were validated by three referral laboratories. The participating laboratories were allowed to use their own preferred method for DNA extraction and mutational analysis and were asked to report the results within 4 weeks. The limit to pass the quality assessment was set at 100% of true responses. In the first round, only two centers did not pass (3%). The two centers were offered to participate to a second round and both centers failed again to pass. == Conclusions == The results of this first Italian quality assessment for KRAS testing suggest that KRAS mutational analysis is performed with good quality in the majority of Italian centers. == Introduction == Mutations of theKRASgene occur in approximately 40% of colorectal carcinomas (CRC), Resminostat and about 90% of these mutations affect codons 12 and 13[1]. KRAS mutations occur relatively early in colorectal tumor progression, and therefore they are usually present in the majority of the transformed cells within a KRAS mutant tumor[2]. The presence of the mutations in a restricted and well defined region of the gene and the occurrence of the mutations in an high percentage of tumor cells facilitates the detection of KRAS mutations in tumor tissues. A number of studies have demonstrated that anti-EGFR monoclonal antibodies are active only in metastatic CRC (mCRC) patients that do not carry mutations of theKRASgene. In particular, analysis of patients treated in phase II and III randomized clinical trials with anti-EGFR antibodies alone or in combination with chemotherapy, in any line of treatment, have shown that anti-EGFR agents increase the response rate and improve the progression free survival (PFS) only in mCRC patients that do not carry KRAS mutations at codons 12 and 13[3],[4],[5],[6],[7],[8],[9]. More Resminostat recently, addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease was also found to result in significant improvements in overall survival (OS)[10]. Following these results, the European Medical Agency (EMEA) approved in 2009 2009 the use of the anti-EGFR antibodies cetuximab Resminostat and panitumumab only in patients with mCRC carrying a wild typeKRASgene. As a matter of fact, this was the first approval of a drug for a solid tumor based on a genetic test. Following the approval of anti-EGFR antibodies for KRAS wild type CRC patients, KRAS testing has become mandatory to choose the most appropriate therapeutic strategy in mCRC. In this respect, both false-negative and false-positive results are potentially harmful for patients. In fact, false positive findings will deprive the patients of the possibility to benefit of an active treatment. On the Resminostat other hand, false-negative patients might be treated with a drug that is not active. In addition, recent findings suggest that administration of an anti-EGFR monoclonal antibody in combination with a regimen containing oxaliplatin to patients with a KRAS mutant tumor might significantly reduce progression free survival[7],[9]. The introduction of a mutational assay Lysipressin Acetate in clinical practice has raised the issue to ensure a rapid and high quality KRAS testing to all patients. Recommendations for KRAS testing in mCRC patients were released by the European Society of Pathology (ESP) in 2008[11]. A recent survey in 14 countries in Europe, Latin America and Asia showed that the frequency of KRAS testing in patients with mCRC increased from 3% in 2008 to 47% in 2009 2009 and 69% in 2010[12]. In particular, the 2010 survey revealed that test results.