We report 2 cases of a foreign body reaction to Radiesse, a semipermanent soft-tissue filler consisting of 30% calcium hydroxylapatite microspheres and 70% carboxymethyl cellulose gel carrier. In one case, injection of this filler provoked a nodule on the columella, which was discovered during rhinoplasty. In the second case, the reaction was revealed during histopathologic examination of the deep section of a surgically removed basal-cell carcinoma. Histopathology showed a foreign body reaction with numerous giant cells and histiocytes, some plasma cells, and lymphocytes. Within this inflammatory reaction, a nonpolarizing exogenous material was identified consisting of numerous, round, uniformly sized, yellowish, extracellular deposits with a crackled appearance. Although many authors claim that Radiesse does not induce any foreign body reactions, we found a number of similar histopathologic pictures in studies describing animal or human auricular area test sites or even in reports of lip nodules, which are a well-known adverse effect after injection of this filler into this site. The histopathologic appearance of Radiesse is particularly distinctive and easily recognizable by dermatologists and dermatopathologists.