Abstract: Heavy metal pollution represents a serious problem facing many of the aquatic organisms. Lead is one of the most toxic elements found in many industrial effluents which are metabolized inside bodies and can cause skeletal deformities by impairing developmental processes and bone formation. This study was undertaken to determine the LC50 of Pb-acetate and detect the effect of 1/10 LC50 exposure on fingerlings of Nile Tilapia (Oreochromis niloticus). Modern and accurate diagnostic methods were used; Scanning Electron Microscopy (SEM) of gills, plain X-ray and Energy-dispersive X-ray Spectroscopy (EDX) of the spinal column to explain the elemental analysis. The results indicated that the 96 h LC50 of lead acetate was 146.8 mg L-1. SEM showed a distinct degeneration in gill filaments and pavement cells with increasing of mucus secretion after lead exposure. X-ray revealed slight dorsal spinal curvature. EDX analysis of the spinal column of treated fish showed decrease in calcium and phosphorus weight percents, on the other hand Pb appeared in treated fish but not in control ones. Finally this study can spot a light on the dangerous effects of lead toxicity in developing of fish and impairment of their skeletal ossification which may lead to skeletal deformities.