Local adjuvant treatment of giant cell tumours (GCTs) of the bone with phenol has led to a significant reduction in recurrence rates. In the current study, the optimal phenol concentration and duration of intralesional exposure were evaluated. Specimens of GCTs were exposed to various concentrations of phenol solution (6, 60 and 80%) for either 1 or 3 min. Following embedding in glutaraldehyde, the tumour cell layers were examined by transmission electron microscopy. Destroyed cell organelles indicated the penetration depth as a sign of denaturation. Incubation of GCT specimens with 6% phenol solution for 3 min resulted in the most tissue damage and the deepest tissue penetration of ∼200 μm. Incubation with 60 and 80% phenol solution reached a penetration depth of only ∼100 μm. Phenol instillation may be used for the treatment of small scattered cellular debris following intralesional curettage; however, it is not suitable for treatment of remaining solid tumour tissue of GCT. The use of high phenol concentrations has no benefit and increases the risk of local or systemic intoxication.