Abstract Background: Hereditary disposition accounts for 10-15% in breast cancers and 20-25% in ovarian cancers, in which 5-10% of women have genomic alteration in breast cancer predisposition genes, BRCA1 and BRCA2, while the rest are likely due to less penetrant genes. In specific ethnicities such as Ashkenazi Jewish, three founder mutations have been identified which covers 95 % of all the BRCA mutations identified in this race. These genes are screened prior to the gold standard Sanger Sequencing in order to reduce cost. Sanger Sequencing, however, still has the limitation on the necessity of laborious processing and results interpretation. Moreover, it limits the number of genes that can be analyzed in one setting. With the use of next-generation sequencing (NGS), identification of hereditary breast and ovarian cancer (HBOC) syndrome associated genes, other than BRCA, can be sequenced at the same time but yet a faster turnover time. This allows more timely targeted risk-reducing strategies and interventions to be implemented for mutation positive carriers and their family members. Methods: In this study cohort, 948 high-risk breast/ovarian patients who met the HBOC selection criteria were recruited for mutation screening by our NGS pipeline. With the inclusion of 90 Sanger-validated known mutation cases, the performance of the NGS pipeline were proven to be comparable to Sanger sequencing. PTEN and TP53, other than BRCA1 and BRCA2, a 4 gene sequencing panel were included in the mutation screening for high-risk patients. Results: The prevalence of BRCA1/BRCA2 germline mutations was 7.28% in our Chinese cohort and 47.8% of the mutation were recurrent mutations. Based on this finding, we further adopted a new workflow by screening the recurrent mutations including founder mutations from Chinese cohort prior to NGS for those who tested negative. In a testing cohort of 343 cases, the recurrent mutation pick-up rate was 3.5%, this implicated a more cost-effective method for mutation screening in the clinical setting. Moreover, the frequencies of PTEN and TP53 were 0.21% and 0.53% respectively in our population with breast and ovarian cases. Conclusion: Taken together, our data demonstrated a strategic upfront screening for recurrent mutations in Chinese population which is highly applicable in most of the diagnostic laboratories. Multi-gene sequencing using the NGS technology will be the upcoming strategies for mutation screening for HBOC patients. Citation Format: Kwong A, Shin VY, Au CH, Law FB, Ho DN, Ip BK, Wong AT, Lau SS, To RM, Choy G, Ford JM, Ma ES, Chan TL. Evaluation on the mutation screening by next-generation sequencing in hereditary breast and ovarian cancer: Implementation of recurrent mutation panel. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-20.