In the large Cucurbitaceae genus Cucumis,cucumber (C. sativus) is the only species with 2n=2x=14 chromosomes.The majority of the remaining species, including melon (C. melo) andthe sister species of cucumber,C. hystrix,have 2n=2x=24 chromosomes, implying a reduction from n=12 to n=7. To understand the underlying mechanisms we investigated chromosome synteny among cucumber, C. hystrix, and melon using integrated and complementary approaches. We identified 14 inversions and aC. hystrixlineage-specific reciprocal inversion between C. hystrix and melon. The results reveal the location and orientation of 53 C. hystrix syntenic blocks on the seven cucumber chromosomes and allow us to infer at least 59 chromosome rearrangement events that led to the seven cucumber chromosomes, including fivefusions, four translocations, and 50 inversions.The 12 inferred chromosomes of an ancestor (AK1-AK12) similar to melon andC. hystrixhad strikingly different evolutionary fates, withcucumber chromosome C1apparentlyresultingfrom the insertion of chromosome AK12 into the centromeric region of translocated AK2/AK8,cucumber C3 originating from a Robertsonian-like translocation between AK4 and AK6, andC5from the fusion of AK9 and AK10. Chromosomes C2, C4 and C6 were the result of complex reshuffling of syntenic blocks from 3 (AK3, AK5, and AK11), 3(AK5, AK7, and AK8) and 5 (AK2, AK3, AK5, AK8 and AK11) ancestral chromosomes, respectively, through 33 fusion, translocation and inversionevents. Previous results thatcucumber C7stayed largely intactduringthe entire evolution of Cucumis are supported. Having the new genome of the closest relative of cucumber, together with that of melon, allows a fine-scale understandingof the mechanisms ofdysploid chromosome reduction not achieved previously. This article is protected by copyright. All rights reserved.