So, Simplify3D, if you're saying the outgoing byte buffer from S3DC to the printer is "the number the user configured plus 1" (like a gun holds n bullets in the magazine plus one in the chamber for a total of (n + 1) ), then perhaps there is a VERY low but non-zero probability of overrunning the printer buffer (63 bytes in RAMBo, 63+1 bytes in Creator).
If the printer buffer declared in building the RAMBo firmware is 63 bytes, and the printer can send (63 + 1), then there is at least the possibility of an overrun. It would be interesting to see if setting the outgoing serial cache to 62 (or a few less even) solves the issue. (To make it look right to the user, take the number displayed in the setup dialog and subtract one when creating the buffer. The result would be (n - 1) in the cache plus the one in the "chamber" (USART outgoing data register) for a total of "n", the number the user entered.
Does the USB link (hardware or driver) support any kind of buffer-full handshaking (like RTS/CTS, DSR/DTR or XON/XOFF on an old style serial port)? Is such handshaking being USED (configured enabled)? Can the link detect errors (ACK/NAK) and retransmit (and tell the difference between an original send and the retransmission)?
I'll let those having the issue try the experiment with the outgoing buffer size configuration. I have not been printing from the PC (usually print from SD Card) enough to run into it. Yet.