We report the repeated isolation for Trichoderma. harzianum, a rare opportunistic pathogen from three sets of each of the following clinical samples; blood serum, skin lesions, sputum and throat of a pediatric ALL patient with neutropenia. The definition of invasive fungal infection requires evidence of the presence of fungal elements in tissue samples, in addition to the isolation of suspected etiologic agent in culture. However, invasive procedures are not always applicable due to several factors, as for example in our case, the poor general status of the individual patient or thrombocytopenia. The present paper also emphasizes the problems encountered in obtaining appropriate samples and diagnosing invasive fungal disease in immunocompromised patient populations, including those with hematological malignancy. Three cases involving T. harzianum, including this one, have been described thus far in the literature. All were fatal and the fungus was resistant to antifungal therapy. A critical review of the other two cases of Trichoderma infections in humans is provided.