The effect of teaching and learning strategies on learners’ performance is important in science education. This study explored the effect of the Predict-Observe-Explain (POE) strategy on Grade 10 Physical Sciences learners’ misconceptions on how salt dissolves in water. A quasi-experimental design was employed in collecting data from South Africa. A t-test and Analysis of Co-variance (ANCOVA) were used to analyse the data. The results show that learners in the experimental group (EG) taught using POE performed better in the post-test than their counterparts in the control group (CG) taught using traditional methods. Also, two new misconceptions were identified, namely: 1) salts dissolve in water when it is in ‘fine’ grains; and, 2) solid sodium chloride is not an ionic compound. These results highlight the need for educators and curriculum developers to include various elements of POE in the curriculum as a model for conceptual change in teaching science. DOI: 10.5901/mjss.2014.v5n4p300