Objective: Serous neoplasms of the female pelvis share a müllerian phenotype. Unlike low-grade serous neoplasms (LGSNs), high-grade serous carcinomas (HGSCs) commonly display p53 mutations. The current study correlates p53 immunoreactivity in peritoneal washings with the cytologic interpretation and histology of the corresponding serous neoplasm. Study Design: Peritoneal washings from consecutive cases of pelvic serous neoplasms were identified (n = 45, 31 HGSCs and 14 LGSNs), with a control population selected from benign resections. Immunoreactivity for p53 was scored as a percentage of positive epithelioid cells by blinded manual cell count. Results: Washings from LGSNs and HGSCs were cytomorphologically positive with similar frequency (57 vs. 77%, respectively, p = 0.15, Fisher’s exact test). Immunoreactivity for p53 was not predictive of morphologic positivity. The percentage of p53-positive cells was higher in HGSCs (47 ± 42%), compared to LGSNs (9 ± 9%) and negative controls (2 ± 2%, n = 10). The difference in p53 immunoreactivity was statistically significant (p < 0.00009, ANOVA). Conclusions: The proportion of p53 immunoreactive cells was higher in cases of HGSCs, reflecting the importance of p53 mutations in high-grade serous tumorigenesis. The presence of p53 staining is not diagnostic for neoplastic cells; however, peritoneal washings are potential specimens in the investigation of serous neoplasia.