Background: Reactivation of hepatitis B virus (HBV) has been widely reported in HBsAg+ cancer patients undergoing chemotherapy, mainly in patients with lymphoma and breast cancer who received Rituximab and Adriamycin based chemotherapy. Reactivation of HBV has also been reported in a few patients who had previous exposure and resolved HBV infection (HBsAg-, HBcAb+). However there is no consensus as to whether prophylactic antiviral therapy should be used for this group, or whether the presence HBsAb plays a further protective role. Methods: We retrospectively and prospectively identified cancer patients undergoing chemotherapy who have HBsAg-, HBcAb+ status. Their HBV DNA levels and serial liver functions were followed. We aimed to evaluate the prevalence of detectable HBV DNA and HBV seroconversion rate after chemotherapy. Results: Between 11/2011 to 6/2013, 124 patients were screened and 51 (41%) had pretreatment HBsAg-, HBcAb+ status. Forty two (82%) patients were of Asian descent; 18 (35%) were males and 33 (65%) were females. Median age was 60 years with a range of 28 to 84 years. Forty seven patients (92%) received chemotherapy for solid malignancies while 4 (8%) received rituximab. Only one patient (2%) had detectable HBV DNA prior to treatment and received baraclude for prophylaxis. Fifteen patients (29%) had HBsAg-, HBcAb+, HBsAb- status, 36 (71%) had HBsAg-, HBcAb+, HBsAb+ status. Serial LFTs were followed over a median chemotherapy duration of 4 months (1 to 18 months). 2 had transient increase; 13 showed persistent but stable elevation related to tumor in the liver; 4 patients were tested for HBV DNA at LFT elevation and were negative. No patient had persistent or worsening LFT related to HBV reactivation. Conclusions: The prevalence of HBsAg-,HBcAb+ cancer patients is very high in South Brooklyn, NY, predominantly in Asian patients. Prevalence of detectable baseline HBV DNA is extremely low, even in isolated HbcAb positive patients and there was no seroconversion of HBV during chemotherapy, irrespective of HBsAb status. Prophylactic antiviral therapy is unnecessary.