This descriptive article describes the use of clinical case-based portfolios in histopathology teaching laboratories in conjunction with virtual microscopy not only to integrate histology and pathology disciplines for first and second year medical students but also to stimulate student engagement, promote self-directed and group-based learning and enhance student-to-student interaction in a structured manner. Portfolios consisted of PowerPoint files encompassing four to five clinical case studies relevant to the topics covered that week. Portfolios integrated study materials provided in the module-specific lectures, clinical skill lectures, and online interactive content. Two sets of portfolios, Individual and Group, were used. Individual Portfolios were completed by each student and uploaded prior to the laboratory session. Group Portfolios were completed by students working together in small groups during the laboratory session with minimal faculty assistance. The functional utility and acceptance of Individual and Group Portfolios among first- and second-year medical students was evaluated using electronic surveys and examination performances. Both first- and second-year students agreed that the use of portfolios in conjunction with virtual microscopy promoted understanding and encouraged discussion of the topics covered during the week and that group members worked well together and contributed to the completion of the portfolios. Performances on the Histology and Cell Biology and Pathology sections on the United States Medical Licensing Examination® (USMLE®) remained consistent and in line with national averages. Overall, use of portfolios promoted peer teaching and contributed towards successful transition to the new system-based integrated curriculum with continued strong performance on the USMLE.