Vatican police have seized documents and computers from the department tasked with maintaining St Peter's Basilica.
It is part of an investigation into potentially illegal dealings.
Officers raided the technical and administrative offices of the prestigious Fabbrica di San Pietro, while Pope Francis appointed a commissioner to run the department temporarily, the Vatican said in a statement.
The commissioner, retired diplomat Mario Giordana, probed the management of the Sistine Chapel choir, which was then placed under investigation by Francis for suspected financial irregularities, Vatican expert Christopher Lamb tweeted.
The Fabbrica raid followed a tip off from the general auditor's office, the Vatican said, without giving further details.
It did, however, mention new rules brought in this month to reduce the risk of corruption in the awarding of contracts.
Italy's Messaggero daily said the raid followed "repeated internal complaints... (of) alleged irregularities in contracts, accounts that did not add up, the same companies always winning the tenders, the suspicion of favouritism".
The Vatican is already facing an ongoing investigation into a London property investment deal that Pope Francis has suggested was not above board.