Background: DNA homologous recombination repair deficiency (HRRD) is a vulnerability that has been exploited for PARP inhibitor therapy. This concept is currently being evaluated in S1400G substudy of LungMAP where HRRD(+) SCC patients are treated with a PARP inhibitor, talazoparib. We assessed the prevalence and characteristics of HRRD(+) SCC patients screened on LungMAP. Methods: All patients receive Foundation One NGS screening platform for enrollment on LungMAP sub-studies. HRRD is defined as genetic alteration predicted to have functional consequence in genes involved in HRR (ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1) but also define a key subgroup based on a set of the best clinically validated genes: ATM, ATR, BRCA1, BRCA2, and PALB2 . Survival was measured from the date of sub-study assignment. Results: Biomarker results were available for 1244 eligible patients screened between June 2014 and October 2017. HRRD was detected in 190 (15.3%) patients, higher than the 9% rate assumed for the design of S1400G substudy. HRRD(+) and HRRD(-) patients did not differ in terms of median age (67 vs. 66 years); male gender (68% vs. 67%); race (85% vs. 84% and 11% vs. 9% for White and Black) or tobacco exposure (94% vs. 95%). BRCA2 alteration was the most frequent of the HRRD gene alterations. Survival was not different by HRRD(+) versus HRRD(-) status (HR[95%CI]: 1.11 [0.91-1.37], p = 0.29). Alterations in BRIP1 (0.58 [0.28-1.23]; p = 0.16), CHK2 (0.43[0.16-1.15]; p = 0.09), FANCM (1.48[0.87-2.52]; p = 0.15) and FANC-A/C/D2 (1.70[1.07-2.72]; p = 0.03) showed a trend in prognostic association. Conclusions: HRRD is frequent in SCC and could define a large subset of SCC for targeted therapy if validated in the ongoing S1400G substudy of LungMAP.