In this review, we discuss the considerable heterogeneity of mesothelioma, the diversity of radiologic and gross presentation, various morphologic features with distinctive histologies and ultimately, we individually describe subsets of tumors characterized by uncommon alterations such as germline mutations, genomic near-haploidization, <i>ALK</i> rearrangement, <i>ATF1</i> rearrangement, or <i>EWSR1::YY1</i> fusion, as well as the implications of these findings on the diagnostic workup. This evidence concerns the gene ALK and mesothelioma.