Cryptococcus is a basidiomycetous yeast responsible for considerable HIV-related morbidity and mortality. A cachectic 26-year-old HIV-positive man with a CD4 count of 103 cells/μl presented with fever, breathlessness, and bilateral lower limb weakness. A brain computed tomography scan could not elucidate the neurological deficit. His blood was sent for culture and serum cryptococcal antigen detection, with the latter testing as negative. By the fourth day of admission, the patient's condition had deteriorated drastically. A lumbar puncture was performed, and like his serum sample, the cerebrospinal fluid also tested negative for cryptococcal antigens. By this time, Cryptococcus neoformans was isolated from the admission blood culture. The laboratory diluted both the serum and cerebrospinal fluid specimens to retest for cryptococcal antigens, and finally, an antigen titer of ≥1:2560 was recorded.