One patient was a 36-year-old male, HIV-positive for 2 years (CD4 T-lymphocyte count 363 cells/mm3; HIV viral load >100,000 copies/ml), and the other a 44-year-old male, HIV-positive for 5 years (CD4 T-lymphocyte count 443 cells/mm3; HIV viral load <75 copies/ml), who had both received rituximab therapy for multicentric Castleman disease. The former manifested with cutaneous KS after 7 days, and the later patient with skin and lymphadenopathic KS flares within 3 months of receiving rituximab. In the control cases both CD3 and CD20 cells were present, with a preponderance of T-lymphocytes identified. In the KS flare specimens, there were only T-cells present with a notable absence of B-lymphocytes. In all control and flare KS cases T-cell subsets showed CD8 > CD4. CD20+ B-cell depletion in the KS flare case of the 36-year-old patient occurred concomitantly with activation of the HHV-8 immediate early gene protein K5. KS flares in both patients were successfully treated with liposomal doxorubicin and valganciclovir.