Background: A collection of 175 melon (Cucumis melo L.) accessions (including wild relatives, feral types, landraces, breeding lines and commercial cultivars) from 50 countries was selected to study the phenotypic variability for ripening behavior and sugar accumulation. The variability of single nucleotide polymorphisms (SNPs) at 53 selected candidate genes involved in sugar accumulation and fruit ripening processes was studied, as well as their association with phenotypic variation of related traits.Results: The collection showed a strong genetic structure, defining seven groups plus a number of accessions that could not be associated to any of the groups (admixture), which fitted well with the botanical classification of melon varieties. The variability in candidate genes for ethylene, cell wall and sugar-related traits was high and similar to SNPs located in reference genes. Variability at ripening candidate genes had an important weight on the genetic stratification of melon germplasm, indicating that traditional farmers might have selected for ripening traits during cultivar diversification. A strong relationship was also found between the genetic structure and phenotypic diversity, which could hamper genetic association studies. Accessions belonging to the ameri group are the most appropriate for association analysis given the high phenotypic and molecular diversity within the group, and lack of genetic structure. The most remarkable association was found between sugar content and SNPs in LG III, where a hotspot of sugar content QTLs has previously been defined. By studying the differences in allelic variation of SNPs within horticultural groups with specific phenotypic features, we also detected differential variation in sugar-related candidates located in LGIX and LGX, and in ripening-related candidates located in LGII and X, all in regions with previously mapped QTLs for the corresponding traits.Conclusions: In the current study we have found an important variability at both the phenotypic and candidate gene levels for ripening behavior and sugar accumulation in melon fruit. By combination of differences in allelic diversity and association analysis, we have identified several candidate genes that may be involved in the melon phenotypic diversity.