Central venous catheter placement for long-term total parenteral nutrition is a well-established practice. Considering the number of placed lines, serious complications are rare but may be life threatening. We report the case of a 6-month-old infant on total parenteral nutrition since neonatal period, as a consequence of severe intestinal insufficiency secondary to extensive intestinal resection for necrotizing enterocolitis. The child was admitted to the ICU with respiratory failure due to bilateral milky pleural effusion 17 days after placement of a left internal saphenous line. Pleural effusion analysis was suggestive of chylothorax, with high triglyceride (722 mg/dl) and low cholesterol (<20 mg/dl). Persistence of pleural effusion, despite adequate treatment, drew attention to other diagnostic hypothesis. Considering that parenteral nutrition solution used is cholesterol free and the child complained of pain when administered bolus through the catheter, the hypothesis of misplacement of the central venous catheter became more likely. Computed tomography scan after contrast administration through the catheter revealed its presence in the epidural space and the ascending route reaching the pleural space. When parenteral nutrition was stopped, the pleural effusion resolved. At the present time, with 2 years of follow-up, the child does not have any complication of this event. This is, to our knowledge, the first reported case of an infant developing bilateral pleural effusion secondary to misplacement of a left internal saphenous catheter.