Serous peritoneal papillary carcinoma (SPPC), though managed according to ovarian cancer therapeutic principles, has been variably considered as an ovarian cancer counterpart, a peritoneal malignancy with distinct characteristics or a cancer of unknown primary (CUP).We systematically reviewed all publications studying molecular pathophysiology, clinical presentation, management and outcome of at least 10 patients with SPPC from 1980 to 2008 in anglophone medical journals and critically analysed the data.Molecular profiling of CUP was performed in eight papers reporting on 211 patients with stage III/IV SPPC by means of immunohistochemistry or PCR-based assays. Twenty-five clinical series, mostly retrospetive, reported management and outcome of 579 patiens with SPPC, in several cases matched to advanced ovarian cancer controls. Though we did not identify statistically significant differences in molecular biology, clinical presentation, management and outcome of SPPC and ovarian cancer cases, some subtle differences emerged: patterns of loss of heterozygosity at several chromosomal loci differed from those seen in ovarian cancer, while the overexpression of the HER2 oncogene was encountered more often. Serous peritoneal tumours affected older patients and were more frequently multifocal or exhibited virulent clonal expansion in metastatic sites. Diffuse micronodular spread formed a high total load of malignancy in omental, peritoneal surfaces, difficult to debulk optimally. Despite effective chemotherapeutic cytoreduction and occasional long-term remissions, SPPC patients survived 2–6 months less than ovarian cancer patients.Patients with SPPC should not be classified in the poor-risk CUP category, in view of the therapeutic and prognostic differences. Still, the assimilation of the SPPC entity by ovarian cancer hindered further research into its genotypic and phenotypic characteristics that may differ from ovarian cancer. Subgroup analyses of large ovarian cancer trials may shed light in this issue.