Some glaciologists have suggested that the West Antarctic Ice Sheet, which is grounded well below sea level, may be susceptible to rapid grounding-line retreat and disintegration. However, until now, geologic evidence of previous ice sheet “collapses” has been lacking. Sediments that have recently been collected from beneath the West Antarctic Ice Sheet at Ice Stream B contain direct evidence of ice-free conditions in the West Antarctic interior during certain Cenozoic intervals, both prior to and subsequent to the development of grounded ice sheets in West Antarctica. The sediments contain rare but diverse microfossils that represent a wide variety of biostratigraphic ages and depositional environments. Microfossils present include relatively common marine and non-marine diatoms and sponge spicules, plus rare foraminifera, nannofossils, radiolarians, silicoflagellates, chrysophyte cysts and palynomorphs. Clasts of Neogene freshwater diatomite demonstrate the former presence of large lake systems in West Antarctica, possibly as part the Cenozoic West Antarctic rift system. Age-diagnostic marine fossils in the sediment include Late Paleogene calcareous nannofossils and planktonic foraminifera, Miocene marine planktonic diatoms and, significantly, late Pleistocene marine diatoms. Relatively common late Miocene diatoms probably reflect marine deposition prior to initiation of a dominantly glacial phase in West Antarctica. It is likely that Pliocene and early Pleistocene diatoms were deposited in the West Antarctic interior during certain warm interglacials, but these have been eroded and transported toward the continental shelf edge during repeated ice sheet expansions. The late Pleistocene diatoms from Upstream B were deposited in the West Antarctic interior basins during a marine phase, subsequent to an ice sheet collapse, during at least one late Pleistocene interglacial. This discovery provides an indication of the complex history of the West Antarctic Ice Sheet, and calls into question some previous interpretations of ice sheet stability based on paleoceanographic proxy data. The results of this study may lend credence to the concern that global warming and rising sea levels in a “greenhouse” earth could lead to collapse of this marine ice sheet during the current interglacial period.