The Human Genome Project has generated a blueprint for the approximately 20, 300 gene-encoded proteins potentially active in any of 230 cell types that make up the human body (human proteome). However, based on the UniProtKB/Swiss-Prot database content, about 6000 of these genes currently lack any experimental evidence at the protein level; for many others, there is very little information related to protein function, abundance, subcellular localization, and interactions. The CHROMOSOME- Centric Human Proteome Project (C-HPP) has been designed to map the entire human proteome in a systematic effort and to will enhance our understanding of human biology at the cellular level and lay a foundation for development of diagnostic, prognostic, therapeutic, and preventive medical applications. As of March 1, 2012, there are 20 international teams, including Royan Institute, focused on 18 different CHROMOSOMEs (www.chpp.org). In Iran, the current efforts are focused on mapping the proteome of human CHROMOSOME Y. The Y CHROMOSOME is unique under many aspects and comprises 95% of the CHROMOSOME’s length. It is always in the haploid state and full of repeated sequences but it is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of Y CHROMOSOME proteome on the platform of genomic Y sequence. Our strategy started with the definition of the proteins coded by the human Y CHROMOSOME, a list of missing/poorly characterized proteins, and proteomic profiling studies to identify those missing proteins.The project is set up to allow for a systematic exploration of the human Y CHROMOSOME proteome using antibody-based proteomics. Within this project, specific antibodies to human Y CHROMOSOME target proteins are being produced using a method involving the cloning and protein expression of protein epitope signature tags.The antibodies are subsequently validated using several approaches including siRNA. The antibodies are now being used to study expression profiles in target cell and in diseased and healthy testis samples. We also align the proteomics data set to the output of RNA-Seq and Real-Time polymerase chain reaction analysis data with defined expression thresholds. Owing to the integration of proteomic, genomic, transcriptomic, phenotypic and pathological data, novel findings are emerging from our studies.Several strategies to maximize the success of the human Y CHROMOSOME proteome project will be presented.