The purpose of the study was to investigate the influence of problem-based learning (PBL) approach on students’ perceptions and attitudes toward the mole concept in Tamale College of Education. The study was quasi-experimental research which employed a non-randomised selection of the research participants who were already organized into intact or pre-existing classes at the time of the study. Out of a total population of 543 first year teacher trainees of the college, 88 were purposively selected for the study. Fourty-four of the trainees were in “A” class and constituted the control group where Traditional Lecture-Based (TLB) approach was applied. The remaining 44 trainees were in the “K” class (experimental group) where the Problem-Based Learning approach was used. The instrument used for the study was the Mole Concept Perception and Attitude Scale (MCPAS) with a reliability coefficient of 0.851.