Eddie died a month before his fourth birthday. Although census records list "chronic consumption" (tuberculosis) as the cause, it has been suggested that Eddie died of medullary thyroid cancer given that: (a) "consumption" was a term then applied to many wasting diseases, (b) cancer is a wasting disease, (c) his father and two of his brothers had several features compatible with the genetic cancer syndrome multiple endocrine neoplasia type 2b (MEN2B), (d) Eddie's thick, asymmetric lower lip is a sign of MEN2B, and (e) 100% of persons with MEN2B develop medullary thyroid cancer, sometimes as early as the neonatal period.
Eddie's body was buried at Hutchinson's Cemetery in Springfield, Illinois. Both parents were devastated. A week after Eddie's death, an unsigned poem entitled "Little Eddie" was printed in the Illinois Daily Journal.
Authorship of the poem was long a mystery with some supposing that Abraham and Mary Lincoln wrote it. In 2012, the Abraham Lincoln Association published an article in their journal that concludes neither parent wrote the poem, and that it was instead an early draft by a young poet from St. Louis. The final line is on the boy's tombstone.
The next child of Abraham and Mary (Willie Lincoln) was born ten months after Eddie's death. After the death of President Lincoln, Eddie's remains were transferred to the Lincoln Tomb at Oak Ridge Cemetery in Springfield.