Method: A total of 68 tumors belonging to 25 patients (17 males and 8 females) with ages ranging between 46 and 80 years (average, 64 years) were studied. KRAS mutation hotspots in codon 12 and 13 were analyzed by polymerase chain reaction and sequentiation. wt-KRAS cases were confirmed with the KRAS StripAssay TM. Objective: Lynch syndrome (LS), the most frequent form of hereditary colorectal cancer (CRC), is caused by germline mutations in the mismatch repair system genes. A recently identified mechanism involving the EPCAM gene is responsible for 6.3 % of MSH2-negative LS cases. We herein explore EPCAM protein expression in LS-associated, MSH2-negative CRCs to evaluate its potential value in the algorithmic approach to LS population screening. Method: We studied a total of 19 MSH2-negative CRCs from 14 different patients in whom we were able to perform a complete germline analysis. Expression of both MSH2 (1:200 dilution, clone G219-1129, Pharmingen) and EPCAM (1:100 dilution, clone Ber-EP4, Dako) was evaluated by immunohistochemistry (IHC). Results: Nine patients showed a deleterious germline mutation that involved the MSH2 gene in three instances and the EPCAM gene exon 9 in six instances. All patients harbouring the EPCAM mutation belonged to the same family. Of the19 CRCs, EPCAM expression loss was seen in only five, all of them were from patients with a germline EPCAM deletion. Conclusion: Due to the high specificity of EPCAM protein loss for identifying LS patients with an EPCAM deletion, we recommend adding EPCAM IHC to the LS diagnostic algorithm in MSH2-negative CRC cases. Objective: Colorectal carcinoma with signet ring cell component (CRC-SRC) is a rare and distinct subtype with little molecular information. We investigated the frequency of BRAF mutation in 28 CRC-SRCs and its relation with clinicopathologic parameters. Method: We categorized tumors into groups 0-9 %, 10-24 %, 25-49 % and >50 % according to signet ring cell component. Genomic DNA was isolated from parafin blocks and analyzed for BRAF V600E mutation by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP). Results: Eleven of cases showed BRAF mutation (39.3 %). The results were also confirmed with sequence. No statistically significant differences were found in clinicopatologic parameters between BRAF wild-type and mutant CRC-SRC. On the other hand, when we adjusted age, gender, percentage of signet ring compenent and stage, we found a statistically significant increased risk in BRAF mutant group compared to BRAF wild-type in Cox regression analysis (HR=7.68, 95 % CI=1.06-55.78, p=0,044) Conclusion: BRAF mutation is frequent in CRC-SRCs. This finding may support its diverse molecular pathogenesis and could have important therapeutic implications for those patients. To clarify the relation of BRAF mutation with clinicopathologic parameters and prognosis in CRC-SRC, studies with multi-instutional larger series are needed.