Latin America, like other areas in the world, is faced with the problem of high arsenic (As) background in surface and groundwater, with impacts on human health. We studied As biogeochemical cycling by periphyton in Lake Titicaca and the mine-impacted Lake Uru Uru. As concentration was measured in water, sediment, totora plants (Schoenoplectus californicus) and periphyton growing on stems, and As speciation was determined by X-ray absorption spectroscopy in bulk and EDTA-extracted periphyton. Dissolved arsenic was between 5.0 and 15 μg L-1 in Lake Titicaca and reached 78.5 μg L-1 in Lake Uru Uru. As accumulation in periphyton was highly variable. We report the highest As bioaccumulation factors ever measured (BAFsperiphyton up to 245,000) in one zone of Lake Titicaca, with As present as As(V) and monomethyl-As (MMA(V)). Non-accumulating periphyton found in the other sites presented BAFsperiphyton between 1281 and 11,962, with As present as As(III), As(V) and arsenosugars. DNA analysis evidenced several taxa possibly related to this phenomenon. Further screening of bacterial and algal isolates would be necessary to identify the organism(s) responsible for As hyperaccumulation. Impacts on the ecosystem and human health appear limited, but such organisms or consortia would be of great interest for the treatment of As contaminated water.