Lettsom was a competent scientist in an age when this was still possible for an amateur.  He was best known as the joint author of Greg and Lettsoms Manual of the Mineralogy of Great Britain and Ireland', which was the most complete and accurate work that had appeared on the mineralogy of the British Isles. First published in 1858, a century later it was still the standard work on the subject, when a reprint was issued.. The mineral lettsomite is named after him.
But his scientific interests were wider, and he corresponded with the most eminent workers in spectroscopy.  He was a member of the London Electrical Society and the author of several papers on geological, electrical and spectroscopic subjects.
He was elected a Fellow of the Royal Astronomical Society in 1849.  In that year he communicated an experiment in bioelectricity: by making a wound in a finger and inserting the electrode of a galvanometer, while placing the other electrode in contact with an unwounded finger, a current was observed to flow.  Lettsom observed that the experiment was repeatable for he had tried it himself.  In 1857 while on diplomatic service in Mexico he sent to the Royal Entomological Society of London some seeds which, when put in a warm place, became "very lively".  The grub responsible had not been investigated scientifically before, wrote Lettsom, and he asked the Society to do so.  These were the celebrated Mexican jumping beans.
While on diplomatic service in Uruguay he brought a 9 inch Henry Fitz telescope for astronomical observations in the southern hemisphere. Owing to unknown problems he sent the telescope back to New York to be checked and adjusted by the telescope maker. The telescope was received by Lewis Rutherford, pioneer astrophotographer and spectroscopist and associate of the Royal Astronomical Society, who helped Henry Fitz on this task. The telescope was left in Uruguay and is in use to this day by the [https://www.aaa.org.uy Uruguayan Amateur Astronomers' Association].