The aim of this study was to establish a scoring method for ploidy analysis using silver in situ hybridisation (SISH) with a chromosome 17 centromere probe. SISH was performed using the Ventana chromosome 17 centromere probe on sections from formalin fixed, paraffin embedded archival cases of complete hydatidiform moles, partial hydatidiform moles and hydropic products of conception with previously established ploidy status (determined by flow cytometry or karyotyping). In order to determine ploidy status, a scoring method was developed based on both the average number of signals per nucleus (ASN) and the percentage of nuclei with three signals (N3S), enumerated in 50 villous cytotrophoblastic and/or stromal cells. The results of four independent observers were compared individually and collectively with previously established ploidy status. There was a highly statistically significant difference between diploid and triploid gestations for ASN (1.86 ± 0.13 and 2.70 ± 0.16 respectively, Student t-test, p < 0.0001) and for N3S (1.14 ± 1.65 and 71.59 ± 14.25 respectively, Student t-test, p < 0.0001). The sensitivity and specificity of the SISH-based assay was 99.1% and 100% respectively for ASN, and 100% and 100% respectively for N3S. A chromosome 17 centromere probe SISH-based assay can reliably distinguish between diploid and triploid gestations. This test has diagnostic utility in distinguishing partial hydatidiform moles from histological mimics.