Advanced ovarian cancers contain 2 distinct phenotypic populations: (a) free‐floating tumor cells in the ascitic fluid and (b) solid tumors. Ascites cells are derived from the solid tumors and spread throughout the peritoneum. Changes in cell‐cell and cell‐extracellular matrix interactions are thought to be responsible for the origin of ascites cells. Since E‐cadherin molecules play a crucial role in the cell–cell interactions in epithelial cells, we investigated the expression of E‐cadherin in those 2 phenotypic populations. Paired samples of ascites and solid tumors were obtained from patients. Both primary tumors and tumor cells isolated from an experimental model showed a marked decrease in E‐cadherin expression in the ascites cells compared to the respective solid tumors. Semi‐quantitative, reverse transcriptase‐polymerase chain reaction (RT‐PCR) was used to determine the steady‐state levels of E‐cadherin‐specific mRNA. Results indicate that the primary tumors had significantly lower levels of E‐cadherin transcript in ascites cells when compared to their solid tumor counterparts. Changes in E‐cadherin expression were also reflected in the invasion capacity of tumor cells in vitro. Ascites cells were 4‐fold more invasive then solid tumor cells, suggesting that ascites cells are a highly malignant phenotype.