Preimplantation genetic diagnosis (PGD) has been applied worldwide for a great variety of single-gene disorders over the last 20 years. The aim of this work was to perform a double-factor preimplantation genetic diagnosis (DF-PGD) protocol in a family at risk for Lynch syndrome. The family underwent a DF-PGD approach in which two blastomeres from each cleavage-stage embryo were biopsied and used for monogenic and comprehensive cytogenetic analysis, respectively. Fourteen embryos were biopsied for the monogenic disease and after multiple displacement amplification (MDA), 12 embryos were diagnosed; 5 being non-affected and 7 affected by the disease. Thirteen were biopsied to perform the aneuploidy screening by short-comparative genomic hybridization (CGH). The improved DF-PGD approach permitted the selection of not only healthy but also euploid embryos for transfer. This has been the first time a double analysis of embryos has been performed in a family affected by Lynch syndrome, resulting in the birth of two healthy children. The protocol described in this work offers a reliable alternative for single-gene disorder assessment together with a comprehensive aneuploidy screening of the embryos that may increase the chances of pregnancy and birth of transferred embryos.