The soil-borne fungus Fusarium oxysporum f.sp. melonis causes significant losses in the cultivated melon, a key member of the economically important family, the Cucurbitaceae. Here, we report the map-based cloning and characterization of the resistance gene Fom-2 that confers resistance to race 0 and 1 of this plant pathogen. Two recombination events, 75 kb apart, were found to bracket Fom-2 after screening approximately 1324 gametes with PCR-based markers. Sequence analysis of the Fom-2 interval revealed the presence of two candidate genes. One candidate gene showed significant similarity to previously characterized resistance genes. Sequence analysis of this gene revealed clear polymorphisms between resistant and susceptible materials and was therefore designated as Fom-2. Analysis of susceptible breeding lines (BL) presenting a haplotype very similar to the resistant cultivar MR-1 indicated that a gene conversion had occurred in Fom-2, resulting in a significant rearrangement of this gene. The second candidate gene which shared high similarity to an essential gene in Arabidopsis, presented an almost identical sequence in MR-1 and BL, further supporting Fom-2 identity. The gene conversion in Fom-2 produced a truncated R gene, revealing new insights into R gene evolution. Fom-2 was predicted to encode an NBS-LRR type R protein of the non-TIR subfamily. In contrast to most members of this class a coiled-coil structure was predicted within the LRR region rather than in the N-terminal. The Fom-2 physical region contained retroelement-like sequences and truncated genes, suggesting that this locus is complex.