Mixed-case WoRdS disrupt performance in word recognition tasks and sentence reading. There is, however, a controversial issue around this finding as the hindered performance could be related to impoverished lexico-semantic access or to lack of visual familiarity. The present experiments aim to examine whether there is a genuine mixed-case effect during lexico-semantic access or whether the effect is driven by a visual familiarity bias (i.e., lack of familiarity may induce a bias toward “no” responses in word/nonword decisions). Participants were presented with same-case vs. mixed-case items in a word/nonword discrimination task (lexical decision) and in a task that requires access to semantic information (semantic categorization). In lexical decision, responses were faster and more accurate to same-case words than to mixed-case words, whereas the nonwords showed the opposite pattern. In two semantic categorization experiments, we failed to find any signs of a case-mixing effect for words. Therefore, the case-mixing effect in word recognition is not due to an impoverished access to lexico-semantic information but rather to lack of visual familiarity.