RubisCO (D-ribulose 1,5-bisphosphate carboxylase/oxygenase) is Earth's main enzyme responsible for CO fixation via carboxylation of ribulose-1,5-bisphosphate (RuBP) into organic matter. Besides the carboxylation reaction, RubisCO also catalyzes the oxygenation of RuBP by O , which is probably as old as its carboxylation properties. Based on molecular phylogeny, the occurrence of the reactive oxygen species (ROS)-removing system and kinetic properties of different RubisCO forms, we postulated that RubisCO oxygenase activity appeared in local microoxic areas, yet before the appearance of oxygenic photosynthesis. Here, in reviewing the literature, we present a novel hypothesis: the RubisCO early oxygenase activity hypothesis. This hypothesis may be compared with the exaptation hypothesis, according to which latent RubisCO oxygenase properties emerged later during the oxygenation of the Earth's atmosphere. The reconstruction of ancestral RubisCO forms using ancestral sequence reconstruction (ASR) techniques, as a promising way for testing of RubisCO early oxygenase activity hypothesis, is presented.