The birth of genes that encode new proteins is a major source of evolutionary innovation. However, we still understand relatively little about how these genes come into being and which functions they are selected for. Here we address this question by generating a comprehensive list of mammalian-specific gene families and analysing their properties. We combine gene annotations and de novo transcript assemblies from 30 mammalian species, obtaining about 6,000 families with varying degrees of conservation across the mammalian phylogeny. We show that the families which arose early in mammalian evolution (basal) are relatively well-characterized. These families are enriched in secreted proteins and include milk and skin polypeptides, immune response components, and proteins involved in spermatogenesis. In contrast, there is a gap in knowledge of the functions of proteins which are specific of certain groups or species (young), despite the fact that they also have extensive proteomics support. Interestingly, we find that both young and basal mammalian-specific gene families show similar tissue-specific gene expression biases, with a marked enrichment in testis. Proteins from both groups tend to be short and depleted in aromatic and negatively charged residues. This indicates shared mechanisms of formation and suggests that the youngest proteins may have been retained for similar kinds of functions as the older ones. We identify several previously described cases of genes originated de novo from non-coding genomic regions, supporting the idea that this mechanism frequently underlies the evolution of new protein-coding genes. The catalogue of gene families generated here provides a unique resource for future studies on the role of new genes in mammalian-specific adaptations.