Purpose of Review <p>Using a model case of a progressive form of paracoccidioidomycosis (PCM), this article comprises a literature review and analyses the Th2 response based on histological images characterizing the acute/subacute forms and highlights the importance of histopathological studies in PCM.</p> Recent Findings <p>PCM is a systemic mycosis endemic in Latin American countries and a growing diagnostic problem as an imported disease in other continents. <i>Paracoccidioides</i>-phagocytic cells relationship comprises a complex multi-factorial host-pathogen interaction that can lead to an asymptomatic/benign infection or progression to the acute or subacute form of the disease. Histopathological studies of the inflammatory process allow the diagnosis and assessment of the quality of the host immune response, as well as the prognosis.</p> Summary <p>Fungal persistence as a facultative intracellular pathogen, low macrophages activation, loose or unstable granulomas with multinucleated giant cells phagocytosing multi-budding yeast cells, large numbers of actively multiplying fungi inside phagocytes and hyper eosinophilia are biomarkers of the Th2 adaptive response in acute/subacute PCM. Histopathological features of the inflammatory process allow evaluation of the quality of the host immune response and are a valuable tool for defining the clinical form of PCM and predicting the prognosis.</p>