Herein, we describe a case of an infertile man detected in postnatal diagnosis with FISH characterization and array-CGH used for genome-wide screening which allowed the identification of a complex rearrangement involving sex chromosomes, apparently without severe phenotypic consequences. The deletion detected in our patient has been compared with previously reported cases leading us to propose a hypothetical diagnostic algorithm that would be useful in similar clinical situations, with imperative multi disciplinary approach integrated with genetic counseling. Our patient, uniquely of reproductive age, is one of six reported cases of duplication of Xp22.3 (similar to 8.4 Mb) segment and contemporary deletion of Yq (similar to 42.9 Mb) with final karyotype as follows: 46,X,der(Y),t(X;Y)(Ypter -> Yq11.221::Xp22.33 -> Xpter).ish der(Y) (Yptel+,Ycen+,RP11-529I21+,RP11-506M9-Yqtel-,Xptel+). arrXp22.33p22.31(702-8,395,963, 8,408,289x1), Yq11.221q12 (14,569,317x1, 14,587,321-57,440,839x0) (c) 2012 Elsevier B.V. All rights reserved.