Hydatidiform moles (HMs) most often occur sporadically and are either diploid androgenetic or triploid. The very rare familial recurrent HMs (FRHMs) have been related to NLRP7 and C6orf221 mutations in the mother. FRHMs are most often diploid with both maternal and paternal origin of the molar genome. We have screened a cohort of 11 women with diploid HMs with biparental contributions to the molar genome with regard to mutations in NLRP7, NLRP2, the NLRP gene most homologous to NLRP7, and C6orf221. This was done in order to reveal if mutations in the mentioned genes play a major role in development of non-recurrent biparental moles. Recently, we have shown that eight of these diploid moles consist of two different cell lines. Only one woman had a mutation in the coding DNA sequence of NLRP7, which most likely contributed to HM development. This woman had non-mosaic repeated moles, and she was the only woman in our cohort with FRHM. We found no unequivocal pathogenic mutations in NLRP2 or C6orf221. Our observations suggest that although NLRP7 and C6orf221 mutations are related to diploid biparental FRHMs, neither of these genes, nor NLRP2, are related to diploid HMs with biparental contributions to the molar genome, in general.