Peripherally inserted central venous catheters (PICCs) are often used for infusion of chemotherapeutic agents, long-term antibiotics or total parenteral nutrition (TPN). We present a case of delayed migration of a PICC inserted for TPN from the superior vena cava into the azygos vein that was not initially recognized on chest radiographs or CT scan. This subsequently led to azygos perforation and extravasation of the TPN solution into the mediastinal, pleural and pericardial spaces. Several anatomical and procedural factors predispose to PICC migration. In this patient, the risk of PICC migration was increased by left-sided insertion and variant azygos anatomy. If a curve in the distal tip of a PICC is seen on a frontal chest radiograph, azygos malposition should be suspected and confirmed with a lateral radiograph, CT scan or catheter injection. This is because azygos malposition increases the risk of venous perforation and needs to be corrected.