The present invention provides methods for single nucleotide polymorphism (SNP)-based killer cell immunoglobulin-like receptor (KIR) gene cluster genotyping using the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. In general, the methods involve amplifying a plurality of target sequences of a plurality of KIR genes, and detecting the presence or absence of a plurality of single SNPs of the plurality of KIR genes by MALDI-TOF mass spectrometry. The invention also features compositions, including arrays of capture primers and optionally extension primers on a substrate surface, and kits, for use in the methods of the invention.