Recent studies revealed that children with developmental amnesia acquired new semantic information. However, they failed to investigate the growth of such knowledge during childhood, and they did not bring evidence concerning the putative role of residual episodic memory in semantic acquisition. This prospective study sought to clarify this issue by assessing both semantic and episodic memory in two amnesic children (RH and KF) with different neuropsychological profiles. We thus applied errorless semantic learning and vanishing cues methods, together with assessments of episodic memory using original recognition tasks within the same protocol. Results demonstrated learning and long-lasting maintenance of multicomponent concepts (comprising labels, categories and features) in both amnesic children. Importantly, episodic memory assessments revealed differential residual abilities in these children, which may account for their respective profiles of semantic acquisition. Thus, RH, who demonstrated residual episodic abilities, acquired normally. However, the learning of KF, who had a massive impairment of episodic memory, remained slower than her controls. In conclusion, even though an episodic impairment may slacken new semantic learning, our research provides new evidence for the de novo acquisition of semantic concepts in childhood amnesic syndrome and strengthens the idea that semantic learning can occur without any recruitment of episodic memory.