Objectives: Veneral Disease Research Laboratory (VDRL) test is an important screening tool for syphilis in pregnancy (because of adverse pregnancy outcomes, particularly congenital syphilis {CS}) and can be combined with the placental histopathological examination in the diagnosis of CS. Thus, we aimed to compare VDRL test results from HIV-positive/HIV-negative pregnant women with relevant historical data and perinatal/placental histopathological findings. Methods: A prospective hospital-based cross-sectional survey of VDRL tests for two study groups (HIV-positive {tests} and HIV-negative {controls} pregnant women) at ante-natal care (ANC)/delivery. A convenient sampling method was used. Relevant (maternal/fetal) historical data were extracted from their case notes, and placentas of reactive VDRL cases were histopathologically examined. Results: We surveyed 145 pregnant women (49 tests and 96 controls). The VDRL tests, for both groups, were not strongly associated with maternal age (p-value = 0.097), booking for ANC (p-value = 0.770), gravidity (p-value = 0.331), and HIV/AIDS stage (for tests only). Notably, one subject from the tests had a reactive VDRL test, and she was in HIV/AIDS clinical stage 2, her baby had microcephaly (fetal head circumference of 31 cm), low birth weight (of 2.4 kilograms), and intermediate APGAR score. Histopathological examination of her placenta showed avascular villi, large hypercellular villi, and obliterative vasculopathy with an onion-skinning pattern in the placental disk. Conclusions: The obstetrical, fetal, and placental histopathological features of the reactive VDRL case were consistent with CS and syphilitic placentitis. Hence placental histopathological evaluation can play a critical role in the diagnosis of maternal/congenital syphilis.