What makes some individuals better able than others to acknowledge opportunities that are not obvious? To address the limits of research studying individual differences without controlling for the characteristics of the opportunities being considered, we conducted an online experiment with 98 biotech entrepreneurs. Building on prior work (Grégoire and Shepherd, FER 2005), we modeled entrepreneurs’ evaluations of opportunities as a function of their prior knowledge, human capital, motivation, self-construct, metacognitive knowledge and overconfidence.