Many missense variants in BRCA1 are of unclear clinical significance. Functional and genetic approaches have been proposed for elucidating the clinical significance of such variants. The purpose of this study was to evaluate BRCA1 missense variants for their effect on both homologous recombination (HR) and non homologous end joining (NHEJ). HR frequency evaluation: HeLaG1 cells, containing a stably integrated plasmid that allows us to measure HR events by gene conversion events, were transfected with the pcDNA3β expression vector containing the BRCA1-wild-type (BRCA1 wild type) or the BRCA1-unclassified variants (BRCA1-UCVs). The NHEJ was measured by a random plasmid integration assay. The assays suggested a BRCA1 involvement mainly in the NHEJ. As a matter of fact, the Y179C and the A1789T variant significantly altered the NHEJ activity as compared to the wild type, suggesting that they may be related to BRCA1-associated pathogenicity by affecting this function. The variants N550H and I1766S, and the mutation M1775R did not alter the NHEJ frequency. These data, besides proposing a method for the study of BRCA1 variants' effect on HR and NHEJ, highlighted the need for a range of functional assays to be performed to identify variants with altered function.