The collision happened just before 5.40pm.
Emergency services were called to the scene near the Willoughton junction.
Four vehicles were involved - a red Mercedes HGV, a black Renault Clio, an orange BMW and a red MG car.
The driver of the MG, a 24 year old woman, died at the scene.
Her family have been informed.
The road was closed and remained closed until this morning.
A police spokesman said: “We are appealing for anyone who was travelling on the A15 north of Caenby Corner immediately prior to the collision and may have seen any of the vehicles involved, or has dashcam footage of the collision itself.
“We would like to hear from you if you have any information that could assist the inquiry.”
There are a number of ways you can contact the police:
Email [email protected] - remember to put the reference incident 328 of 14/12 in the subject box.
Via the non-emergency number 101, quoting incident 328 of 14/12.
Through the independent charity Crimestoppers anonymously on 0800 555 111 or online at crimestoppers-uk.org.