We previously showed that FRA7G, an aphidicolin-inducible common fragile site at 7q31.2, colocalized with the common region of loss of heterozygosity (LOH) in a number of different tumors. Based on the sequence analysis of 150 Kb in the FRA7G region, we identified four new polymorphic microsatellite markers. In this article, we have used these four microsatellite markers and eight additional markers from 7q22-32 to analyze the breakage and loss of the region surrounding FRA7G in 49 invasive epithelial ovarian cancers and three borderline ovarian tumors. No allelic loss was detected in the ovarian tumors of borderline malignancy, but 71% (35/49) of the invasive tumors showed LOH at one or more loci in the region analyzed. Of the 12 markers analyzed, most of the markers exhibiting a high frequency of LOH were within FRA7G, and the highest frequency of LOH was seen with the new marker 7G14 (37%, 15/41). Breakpoint analysis in tumors with LOH demonstrated that the frequent loss of DNA sequences seen within the FRA7G region was due to frequent small interstitial deletions and not a result of loss of the whole fragile site region. These findings indicate that FRA7G does play a role in the breakage and loss of 7q sequences in invasive ovarian cancer. In addition, the newly identified markers enable us to further delineate a smallest common region of loss in invasive ovarian tumors to a 150-Kb region flanked by markers D7S486 and 7G14.