Loss-of-function germline mutations inBRCA1(MIM $113705) confer markedly increased risk of breast and ovarian cancer. The full-length transcript codifies for a protein involved in DNA repair pathways and cell-cycle checkpoints. SeveralBRCA1splicing isoforms have been described in public domain databases, but the physiological role (if any) ofBRCA1alternative splicing remains to be established. An accurate description of ‘naturally occurring’ alternative splicing at this locus is a prerequisite to understand its biological significance. However, a systematic analysis of alternative splicing at theBRCA1locus is yet to be conducted. Here, the Evidence-Based Network for the Interpretation of Germ-Line Mutant Alleles consortium combines RT-PCR, exon scanning, cloning, sequencing and relative semi-quantification to describe naturally occurringBRCA1alternative splicing with unprecedented resolution. The study has been conducted in blood-related RNA sources, commonly used for clinical splicing assays, as well as in one healthy breast tissue. We have characterized a total of 63BRCA1alternative splicing events, including 35 novel findings. A minimum of 10 splicing events (Δ1Aq, Δ5, Δ5q, Δ8p, Δ9, Δ(9,10), Δ9_11, Δ11q, Δ13p and Δ14p) represent a substantial fraction of the full-length expression level (ranging from 5 to 100%). Remarkably, our data indicate thatBRCA1alternative splicing is similar in blood and breast, a finding supporting the clinical relevance of blood-basedin vitrosplicing assays. Overall, our data suggest an alternative splicing model in which most non-mutually exclusive alternative splicing events are randomly combined into individual mRNA molecules to produce hundreds of differentBRCA1isoforms.