Summary Inherited factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder mostly caused by point mutations. Large genomic re‐arrangements at F7 locus could account for a fraction of mutant alleles that remain unidentified after DNA sequencing, because they escape conventional polymerase chain reaction (PCR)‐based techniques. We report the first systematic screening of F7 for large re‐arrangements, by semi‐quantitative multiplex PCR of fluorescent fragments targeting the 9 exons and the promoter region. A well‐characterised cohort of 43 unrelated patients either apparently homozygous for a F7 point mutation or carrying at least one unidentified F7 mutant allele participated in this study. Two large F7 re‐arrangements were identified in two FVII‐deficient pedigrees, including a discontinuous deletion involving two distinct portions of F7 whose proximal and distal end junctions were characterised. A simple and efficient method for the routine detection of gross alterations of F7, which accounted for 2.3% of mutant alleles in our sample, is now available in inherited FVII deficiency. This test should complement conventional PCR‐based techniques not only in unsolved cases, but also where inheritance pattern analysis is not achievable.