The precipitation of calcium oxalate monohydrate (COM) at phospholipid monolayers confined to the air/water interface is observed in situ with the aid of Brewster angle microscopy. COM crystals appear as bright objects that are easily identified and quantified to assess the effects of different conditions on crystallization. Crystal precipitation was monitored at monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in liquid condensed (LC) and liquid expanded (LE) phases. Within the LC phase, higher pressures reduce the incidence of crystallization at the interface, implying that within this phase precipitation is enhanced by higher compressibility or fluidity of the monolayer. Precipitation at biphasic LC/LE and LE/gas (G) monolayers was also studied. COM appears preferentially at phase boundaries of the DPPC LC/LE and LE/G monolayers. However, when an LC/LE phase boundary is created by two different phospholipids that are phase segregated, such as DPPC and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, crystal formation occurs away from the interface within the DPPC LC phase. It is suggested that COM growth at phase boundaries is preferred only when there is molecular exchange between the phases.