Solid pseudopapillary tumors (SPTs) of the pancreas have characteristic morphologic features and show consistent beta-catenin abnormalities and loss of E-cadherin protein. The loss of cell-to-cell adhesion is thought to contribute to frequent cystic degeneration and pseudopapillae formation. p120 regulates E-cadherin and is responsible for its degradation.A tissue microarray of 20 cases and whole sections from another 9 cases of SPT were stained with p120, beta-catenin, and E-cadherin. All 29 cases showed cytoplasmic and nuclear staining for beta-catenin, loss of E-cadherin, and decrease or loss of p120 membrane localization but cytoplasmic staining instead. Loss of membrane p120 staining with relocalization to the cytoplasm was seen in cystic and solid areas of the tumors. This study indicates that p120 expression in SPTs is abnormal and loss of E-cadherin is probably consequent on p120 loss or decrease. Aberrations and other alterations of the E-cadherin gene are unlikely to be responsible for the loss of E-cadherin in SPTs.