Acral lentiginous melanoma (ALM) originates on non-hair-bearing skin of the palms, soles and nail apparatus, areas that are usually shielded from sun-exposure. The absolute incidences of ALM are similar among world populations with different skin colors. Different from the more common cutaneous melanomas, ALMs genomes have much few point mutations, more abundant complex structural variations and copy number changes that can be detected in the earliest stage of progression, and a different spectrum of driver mutations. These suggest that ALM genomes likely have distinct trajectories of evolution, and the research of which can provide valuable insights in understanding this melanoma subtype. However, such investigation has been hindered because its low incidence makes it difficult to obtain suitable patient samples with different progression stages. In this project, we propose to comprehensively characterize the genomic evolution of individual ALMs. We curated a cohort of FFPE (formalin-fixed paraffin-embedded) samples from ALM patients, all of which have at least 2 out of the 3 ALM stages (melanoma in situ, invasive and metastatic melanomas) available. From our pilot study, we observed several distinctive evolutionary features. Specifically, primary ALM clones from the same patient can be highly divergent; oncogenic mutations such as BRAF V600E can arise late during progression; and ALM cells can disseminate at variable timing during progression. We plan to further research these evolutionary features by scaling up our sequencing dataset. Our study of the genomic evolution, heterogeneity and metastasis of ALMs will shed light on the diagnostics and therapeutics of this malicious melanoma subtype.