While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.