Due to the antiquity of cultivation of various cultivars of melon and cantaloupe in Iran, it seems that there are valuable and rich genetic resources of this plant in Iran. In this study, in order to investigate the genetic diversity of 40 melon and cantaloupe cultivars in Iran and Afghanistan, which were collected from the central regions of Iran and also from southwestern Afghanistan, was performed using ISSR molecular markers and some morphological characteristics. According to the obtained results, 12 ISSR markers produced polymorphic bands with a clear band pattern. A total of 150 bands were created, of which 95 bands showed polymorphism (62.44% diversity). The strips were scored with the numbers zero for the absence of the bar and one for the presence of the bar. The results of cluster analysis (HCA) and modification to principal components (PCOA), were able to divide the genotype into five groups based on shape and characteristics such as winter and late-ripen melons, medium-ripen and sweet melons, early melons, including cantaloupe and warm melon... Principal component analysis was in most cases consistent with cluster analysis; But the molecular results did not completely match the morphological results. The findings of the analysis divided the morphological traits of individuals into five groups, the first group consisting of nine Iranian and Afghan melon genotypes, which usually had long, thin skinned form and medium ripening, and the second group, five Afghan melon genotypes with late ripening, winter-ripe and thick skin and flesh. The third group of eleven Iranian and Afghan melon genotypes were usually medium-sized, thin-skinned and elliptical-shape melons. The fourth group consists of two genotypes, both of which are Iranian. The common characteristics between these two melons are having small seeds, small melons, early-ripen and tasteless. The group of five or thirteen genotypes were often grouped based on the similarities between thick and soft flesh, spherical shape and large seeds. Keywords ISSR, Morphology, Genetic diversity, Melon, Genetic diversity