In breast cancer cells, malignant behaviors such as migration depend on calcium release from intracellular storage sites. This process is mediated by phospholipase C (PLC)-γ1, which is typically activated by receptor tyrosine kinases. However, PLC-γ1 can also be activated by phosphatidic acid, a product of phospholipase D (PLD). PLD expression and activity are associated with breast cancer cell invasion and migration, but it is unknown whether PLD is needed for PLC-γ1-mediated calcium release. A recent study investigated this possibility in two human breast cancer cell lines. The researchers found that treating the cells with the PLD inhibitor FIPI prevented PLC-γ1-mediated calcium release and cell migration without affecting PLC-γ1 directly, indicating that PLD is indeed connected to migration-related calcium release in breast cancer cells. Silencing of a specific form of PLD, PLD1, also inhibited PLC-γ1-specific calcium release, demonstrating that PLD1 was important for FIPI’s effects. More work is needed to determine the specific mechanism, and the results should be verified in additional breast cancer cell lines, but the findings reveal a previously unrecognized link in breast cancer signaling and may have implications for breast cancer treatment.